Spasticity is a poorly understood phenomenon. The aim of this paper is to understand the effect of spasticity on daily life and identify bedside strategies that enhance patient's function and improve comfort. Spasticity and clonus result from an upper motor neuron lesion that disinhibits the tendon stretch reflex; however, they are differentiated in the fact that spasticity results in a velocity dependent tightness of muscle whereas clonus results in uncontrollable jerks of the muscle. Clinical strategies that address function and comfort are paramount. This is a secondary content analysis using a qualitative research design. Adults experiencing spasticity associated with neuromuscular disorder were asked to participate during inpatient acute rehabilitation. They were asked to complete a semistructured interview to explain and describe the nature of their experienced spasticity on daily basis. Spasticity affects activities of daily living, function, and mobility. Undertreated spasticity can lead to pain, immobility, and risk of falls. There were missed opportunities to adequately care for patients with spasticity. Bedside care strategies identified by patients with spasticity are outlined. Uses of alternative therapies in conjunction with medications are needed to better manage spasticity. Patient reports on spasticity are important and should be part of clinical evaluation and practice. Disability can have devastating effects on people's lives. It is estimated that about 15% of people in the world live with different types of disabilities . Martin The most common understanding of spasticity has roots in Lance's study . In thisOne of the essential functions of the human motor system is to determine the correct joint positions and movements, specifically, a motor program, required to carry out the daily activities of life. In addition, a motor system must integrate the motor intention of the individual with the muscle tone and body position information from the musculoskeletal system to determine that motor program. Muscle tone refers to continuous partial resistance that prevents full relaxation of voluntary muscles. This resistance is felt due to the elasticity and compliance of the tissue when a limb is moved through passive range of motion . This paHomeostasis of normal muscle tone is disrupted for many reasons. In some instances, pathways to maintain muscle tone are disrupted due to injury-producing lesions in motor neurons. Neurons that connect the brain to the spinal cord are known as upper motor neurons (UMNs), whereas neurons that connect the spinal cord to muscles are called lower motor neurons (LMNs). From the brain, upper motor neurons provide the movement instructions transmitted through the lower motor neuron to the muscles. When the lower motor neurons are damaged, the result is twitching of contiguous fibers (fasciculation), muscle weakness, and atrophy . When thThis is a critical review of the literature that clarifies neurological disorder of spasticity, hypertonia, and related terms. Following types of hypertonia are clarified by outlining the pathophysiology for spasticity and clonus. Neurological terms such as spasticity and hypertonia and associated terms require clear understanding and interpretation in clinical practice for safe patient care.Hypertonia is an “umbrella term” that describes any condition leading to tight or stiff muscles. Many clinicians use the term hypertonia interchangeably with spasticity; however, spasticity is a type of hypertonia that is velocity dependent or in other words is increased with movement, though spasticity can be present at rest. In clinical practice, spasticity is often confused with other conditions such as clonus and rigidity. The velocity dependent aspect of spasticity distinguishes it from rigidity, which is not velocity dependent. Rigidity is a symptom seen with basal nuclei lesions, such as Parkinson's disease. With rigidity, muscles exhibit the same degree of tightness regardless of the amount of movement or sensory input . SpasticThe tight, stiff muscle experienced with hypertonia is a symptom of upper motor neuron dysfunction. Nerve impulses are normally relayed from the UMN to interneurons in the spinal cord and then through the LMN to muscles ; UMN damSpasticity is a part of a disabling UMN syndrome. The UMN lesions decrease the inhibitory drive in the corticospinal tract to produce spasticity. Spasticity is generated through local activation of muscle spindles, but the propagation and manifestation of spasticity require involvement of the central nervous system , 14. TheSpasticity is a sensory-motor phenomenon. The new definition from the Support Program for Assembly of a Database for Spasticity Measurement (SPASM) project defines spasticity as “disordered sensory-motor control, resulting from an upper motor neuron lesion” , page 72The pathophysiology of spasticity and clonus is separate but interrelated. Clonus is generally more easily induced in the ankles and feet. When the ankle is dorsiflexed, muscle spindles are stretched in the gastrocnemius muscle which is sensed by sensory receptor Ia and impulses are sent to the spinal cord where it synapses on the alpha-motor neurons leading to more activation of alpha neurons to the gastrocnemius and soleus. Contraction of the gastrocnemius and soleus leads to plantarflexion. Cycles of plantarflexion and dorsiflexion follow as the gastrocnemius and soleus contract quickly and then relax and stretch in a repeating loop . CompetiWith an UMN lesion leading to spasticity and clonus, alpha neurons are activated too much with the loss of inhibition from corticospinal and dorsal reticulospinal corticobulbar pathway and excitation from vestibulospinal and medial reticulospinal pathways . Highly Spasticity and its consequences negatively influence quality of life. Management of spasticity is an important care issue in neuroscience because it can affect quality of life. Very few first-person accounts of spasticity are available. Most literature has focused on the quantification of symptoms but patient's input is lacking , 23, 24.Despite the fact that spasticity is a lived experience, there are very few studies on patient accounts and perception of spasticity. Bhimani et al.  and MahoSpasticity is a fertile area for research. Clinical outcome measures to assess spasticity at the bedside cannot completely account for the myriads of spasticity experiences. Understanding of spasticity and clonus from patient perspective and how it affects daily life is needed for clinical understanding and bedside practice.The purpose of this study is to understand the effect of spasticity and clonus on daily life and identify bedside strategies that enhance patient's function and improve comfort.What are spastic patient experiences of activities of daily living, function, mobility, comfort, and pain?to identify missed opportunities for care during inpatient rehabilitation stay;to identify bedside strategies for care in practice.Specific aims wereThis is a secondary analysis of the original longitudinal qualitative study to identify strategies that impact spastic patient's activities of daily living, mobility, and comfort.The study setting was a 31-bed acute rehabilitation unit in a large nonprofit tertiary-care hospital and a stand-alone rehabilitation center with 56 beds both located in a metropolitan area of the Midwestern United States. Both settings were at Commission on Accreditation of Rehabilitation Facilities (CARF) certified for spinal cord injury (SCI). Administrative and institutional review board permissions were obtained from both facilities. A total of 23 participants were recruited with neurological disorders associated with spasticity. Out of 23 participants, the first 10 participants were recruited from the hospital-based rehabilitation unit. The remaining 13 participants were recruited from the stand-alone center. The majority of patients were Caucasian (83%), with the diagnoses of spinal cord injury (61%), stroke (17%), cerebral palsy (13%), and multiple sclerosis (9%). About equal number of men (48%) and women (52%) were recruited, with a majority of participants (57%) under the age of 45 and the rest were under the age of 65. Neurological deficits included inability to perform ADLs independently (100%) and mobility impairments where 22% needed some assistive device while 78% were wheelchair bound, of which 13% could not move upper or lower extremities. All participants' hearing, vision, and speech were preserved.The original research study focused on understanding spasticity over time. Subjective understanding of spasticity was extracted from responses to a daily open-ended question about spasticity. The purpose was to allow patients to freely express their spasticity experiences nested in daily routines. In addition to daily open-ended question, twice a week patients were asked in-depth questions to capture changes in spasticity through words during their routines of daily living. Participants were followed up for seven days in the inpatient rehabilitation setting.During data analysis for the original study, it was apparent that the participants provided large amounts of data. Therefore, a secondary data analysis was undertaken guided by the current research question. Colaizzi's method , 27 guidLincoln and Guba's  criteriaIn the morning when the aides are turning me over, when they turn me, they have to turn me so many hours every night. Those are when I'm going through my worst spasms then in the middle of the night and late in the afternoon. #101Experiences of spasticity were embedded in the circadian rhythm. Spasticity experiences were not bounded by the days or hours. Instead, the best clues for understanding spasticity may be understood through rhythms of one's biological clocks and daily activities of life habits based on the institutional routine during acute rehabilitation. At a glance, spasticity may appear to be unreliable and unpredictable; however, closer look reveals that experiences of spasticity appear to be linked with activities of daily rhythm, as these participants become cognizant of how certain things affect their symptoms of spasticity.Spasticity should be, I think be termed as anything that any involuntary muscle movement that interferes with a person's daily living and that is the exact opposite of what they tell their body to do. #201It made it difficult for dressing, getting up and all that stuff, that's all I know, that's the big change. I can't go anywhere I want, because I just can't get up and go, that's my change area. I can't normally do what I normally do. #141Patients' spasticity fluctuated throughout the day. Individual participants reported that their life revolved around activities of daily living (ADL). Most of them spent considerable amount of time dealing with their routines. ADL routines either in the morning or at bedtime require considerable energy and participants often felt frustrated because the body did not respond on command.I'm always afraid I will kick whoever getting me up and stuff. #151 Like last night I told the RA (assistant) to get out of the way and zap I was kicking and waving on my bed and she was out of the way. She said you almost kicked me. I replied, Yes, but I gave you lead time, you know not to come close to me when I'm having a spasm (clonus). I don't think anybody is ever going to understand that unless, well maybe in 500 years. # 181Since increase in clonus and spasticity activity may be triggered by simple touch, patients felt helpless and troubled. Some participants in the study reported being afraid that their condition might cause an injury to their caregivers during ADL.Missed Opportunity. Most participants wanted their caregivers to slow down while assisting them with ADLs. Often they felt that caregivers were so engaged in “tasks” that they lack patience with them. They felt rushed in their care which compromised their sense of control over ADLs.A little more patience. I think they lack a lot of patience. Some of them, not all of them. You have some who come in that just lack patience with the patients that are here. #191A lot of times they seem like they're in a rush and a lot of them like say, for shaving, cleaning their ears out or whatever it is, you know stuff like that that is an every-day thing. #171Just that it's an out of control feeling. Things kind of jerk up and tighten up a little bit. If I didn't have seat on my chair, I'd probably be laying on the ground. #151Physical cost of spasticity is paramount as mobility limitations and limb impairments reduce their chances to fully engage in their lives. Spasticity patients struggle with mobility, function, and transfer issues. Although some participants had families and jobs, they were dependent on others for their daily routine care. This dependency on others can diminish their quality of life. Mobility impairments leading to possible falls are a genuine concern. Gait instability or violent tremors can contribute to the risk of fall. Fear of falling is a genuine worry because muscles do not respond on command.I also think that the way that your chair is made effects that. Because if you can move around and put your legs in a different position when you're feeling tense, I think that would help a lot. #161I don't know, because I'm sitting upright all the time and I'm not laying back. The more lay back the more my spasms kick in. If I'm sitting up, they're not bad, if I lay back, they're bad. #131Use of a wheelchair did not always make them feel secure; often issues with body positioning relative to the chair were a concern as participants reported.Missed Opportunity. Common concerns reported by patient participants were that their caregiver did not understand their mobility restrictions. Just because they were in a wheelchair, they did not perceive themselves mobile as given that spasticity affected their entire body.I think they either should, like say like somebody ain't got the use of their hands and that they should after the aide get done with you, they should help you down to the elevator you got to go down. Like me, I can't push the buttons or stuff like that I think they should follow them down. Right now what I'm doing I'm going myself and then just seeing if there's somebody there to, I'm asking people walking by to turn the elevator on. #191During later in the day they (clonus) too get more frequent so I guess that's about all on that one… Oh, sometimes they wake me up. Then I have to get repositioned and get some ice. #131There's nothing else you can think about but the pain that's going through your arms and through your legs, there's not too much you can do about it. # 191If muscles are incredibly tight and I haven't stretched at all, I do experience quite a bit of pain… I'm always tired so I have to really concentrate in order to get my body to do anything that I want it to do. #201Right now I'm in a real bad sharp pain radius and it's really killing me. It's really testing me and I just want to go somewhere and bark I'm in pain right now. #141We were sitting by the parking lot in the shade and I had quite a few (clonus). I decided to go in because I was drained, I couldn't even drive (wheelchair) I was drained so much. Like I'd run a marathon. #181Pain and insomnia are intricately linked in this population due to muscle tightness. The patients experiencing clonus may have sleep issues as constant jerking motion may not allow them to fall asleep easily. On the other hand, spasticity patients simply cannot relax due to tight muscles. Therefore, aggressive management of the troubling symptoms is needed to improve quality of life. This uncomfortable symptom experience of insomnia can lead to fatigue, which in turn creates stress and further increases spasticity. Therefore, caregivers must be cognizant of all these interrelated clusters of symptoms and address these issues in a comprehensive manner.Once I get stressed or if there is a lot of stuff going on, my tone will automatically increase. #81I like to talk on the phone, it relaxes me… usually I talk to my parents and my friends, like today I'm going to talk to this friend of mine that I haven't talked to in a long time. #161Where they have this little Chinese herbal medicines or needles in different parts of your body this is an energy movement or guided imagery or things like that. #151The most prominent finding of this study relates to the impact of daily stressors on the spasticity experiences. Most patients were very vocal about the negative impact of stress from emotions such as being angry, feeling rushed, and experiencing anxiety. To combat this, some participants took refuge in meditation, acupuncture, and prayers.Missed Opportunity. Most spastic patients require stretching throughout the day to manage spasticity. If not done with frequent intervals, it led to suffering and pain.So if you don't move then you come out and try to move it ain't going to work. I mean the muscles are all this cramped up. That's why they had a hard time trying to stretch me out I was screaming a lot, because all the muscles were all the way you left me lay bent up so try to straighten something when you're bent, laying in there like that, that's all I can say on that. #141I started realizing I had good days and I had bad days and when I really noticed it is when I would get a UTI and then my spasticity would be terrible and I would be so uncomfortable. #81I do have a UTI now, an upper urinary tract infection and that, in me, can set off spasms (clonus). I'm prone to colonizing if they put me on antibiotics. I was worried about that on the last week because my UTI wasn't clearing up. But they're managing it with something else and I drank a couple of full water bottles during the day, which makes me have to go and I think it's clearing it out is what's happening. #181Comorbidities also seemed to affect spasticity. One participant was experiencing urinary tract infection and a kidney stone. There was an increase in clonus activity where spontaneous series of uncontrollable tremors were noted without provocation. Spasticity was noted to increase as well.Missed Opportunity. Clinician often used vocabularies that patient did not understand. One participant did not know that the “complete” and “incomplete” spinal cord injury have different connotation in medical jargon.I was thinking it meant that the nerves is there  and they going to connect, if you strong enough, they going to start connecting to each other, that was what I was thinking it was, connecting to each other and if I got the strength to do it, it will come together and you will be ok, I got to have the strength and the willpower and I got to make it happen and I can't make it happen…That ain't true, it don't work that way, it do not work that way. #111To sum it all up, I think doctors should give their patients options and strategies for coping with spasticity based on what the patient says versus what is happening clinically. #201I think there should also be a more holistic approach like deep breathing and stuff like that seems to help me and like being in warm water. Right now it's more of a clinical, what can we do with drugs to treat this condition mindset. I think a lot more can be done with natural medicine and that's what I'm hoping anyway. #71Spasticity is managed by physical therapy, drugs, and surgery. Oral antispasmodic medications such as baclofen, tizanidine, and dantrium are used for initial management of spasticity and clonus while intrathecal baclofen may be used for severe symptom management , 30. UseThey are laying there, my left leg I can feel more in that leg than in the right leg. It feels so stiff so when they move them I can feel the pain in it when they start doing the exercises. They are supposed to do it every so often when I'm lying down, especially early in the morning and before I go to bed at night but I don't know what kind of schedule they have here. Every schedule is always different, you know when the aide comes in so this morning she did a little bit of it, but I don't think she did enough of it.Especially in the morning I like to stretch and it takes me a while to get up or feel like I want to get up and get moving because I like to stretch. #151It's a lot different when I'm going to physical therapy that they stretch a lot better than the aides do it. My leg feels a lot better, I can feel the tightness going away, which the aides do it, they don't, the tightness is still there when I get down to therapy and I can feel it in my legs as I'm going down there. #91Range of motion and stretching is a corner stone of spasticity management. Since muscle tightness causes pain and contractures, most participants were on scheduled physical therapy and stretching routines. Some stretching was done as a part of activities of daily living while intentional stretching was embedded throughout the day. Participants felt that this care strategy was particularly important to maintain comfort and function.I think the water just holds you up so you don't have to concentrate. They have had things that hold your head up so you barely have to do anything so the muscles completely relax, that's when I would say I am the least spastic or when I am in any type of water, I'm a lot more relaxed than normally. #161“What makes it better is generally environmental factors that just hot and cold and not having too much going on.” #31Over time participants had figured how to self-manage their symptoms of spasticity and clonus. They shared the fact that keeping sudden noise and touch to minimum is important in preventing inducement of clonus and spasticity. Pool therapy with warm water was desired and seen as a good relaxation therapy.Lately, I've been waking up in the morning with severely cramped arms to the point I couldn't move again. Not this morning, every morning for about a week prior, I've been waking up with arms just clenched to my chest and I couldn't move them until I got range in the morning and then they seemed to loosen up a little bit. One thing I did different last night when I didn't wake up this morning with the cramped arms, was I wore a sweatshirt to bed. I was hot sleeping, the room is cool, air conditioned, it was cold outside last night and I wore my sweatshirt to bed and it kept my upper torso warm and I woke up with basically no cramping this morning so I'm going to keep doing that from now on. #181The cold pack does help at night. #121A loud noise you know something like that…I'm going to jump now, I think that would change if I didn't have so much spasticity. #30Most participants identified warm temperature helpful in management of spasticity; however, one participant reported use of ice at night time to facilitate sleep.If I'm relaxed, I'm happy, if I'm upset, I'm more tense, at least for me. Mood really changes it for me. I think when you're more relaxed, it's different. I think more people should, or the doctors should recommend acupuncture or something for relaxation, I don't know if I would do it but if I had a doctor's order, I might. My roommate does it and she really likes it, she's like you should try it. #161We're going to waste a lot of money by going backwards instead of trying to go forward and try some of their natural herbs and the way they do the acupuncture, it's been helping a lot of other people. And, they've been doing it a long time before we even thought about it. #20My mother-in-law is teaching me meditation and I'm going hypnotism too at the same time. Those two things with the medication is kind of keeping me in save. That's where I am right now. Those three things is going on and my family. My family is a big help. #111Feeling negative or depressed was reported to increase spasticity. Most participants acknowledge mind-body connections and felt that their care strategies should include more than “western medicine” approach. Participants shared utilization of alternative medicine in conjunction with western medications.I don't think anybody is ever going to understand that unless, well maybe in 500 years, you can't live inside another person's body, you don't know what you're going through and it's very difficult to explain to other people… The only to experience it is to have to happen to you, I think. #181Someone who hasn't experienced severe spasticity has no frame of reference so their perception of their spasticity may be more severe than the clinician thinks… in my opinion, it would be very important for doctors to look at a patient based on what their baseline is as far as spasticity. #201Most patients considered their understanding to be unique and individual, as the essence of spasticity was learned through personal accumulated experiences over time. There was a strong sense that, to understand spasticity, one must live it to understand the pain and suffering. (Page 33).to establish a strong relation with a certain question, phenomenon, or notion, the researcher cannot afford to adopt an attitude of so-called scientific disinterestedness. To be oriented to an object means that we are animated by the object in a full and human sense. To be strong in our orientation means that we will not settle for superficialities and falsitiesResearch provides the guidance for clinical issues in practice. Qualitative researchers are required to understand human meaning associated with a phenomenon to provide better health care experiences. As Van Manen  pointed, (Page 63).the “data” of human science research are human experiences. It seems natural, therefore, that if we wish to investigate the nature of a certain experience or phenomenon, the most straight forward way to go about our research is to ask selected individuals to write their experiences downThe understanding of a phenomenon is socially, temporally, and contextually bound and dependent on the individual's realities. The essence of a phenomenon may be universal but its varied interpretation provides some degree of depth and richness of those experiences. Interpretation is fluid, based on context and temporal nature of the experiences. Van Manen  further The results of this study indicate that spasticity is a lived experience. The richness of this lived experience captures its essence in the context of health. The lived experience of spasticity calls for the eudemonistic approach of well-being. This incorporation of patient accounts captures the essence of their symptom experiences, which in turn assists clinicians in matching their practice with patient experiences. This clarity and congruency have implications for the quality of life for patients who suffer from spasticity. Therefore, this study provides glimpses into the lives of spastic patients through their own lived experiences. Although researchers and clinicians want accurate definitions, precise measurement tools, and state-of-the-art interventions to help human suffering, individuals who are suffering from spasticity, their input is critical for evidence-based practice. The clinicians face many challenges when caring for spasticity patients as this population experiences myriad of sensations due to neurological deficits. Some patients may be experiencing L'Hermittes sign, which could be part of the multiple sclerosis or spinal cord injury experience, where patients describe a sensation of electric shock going through their body . Others Spasticity is often accompanied by uncomfortable pain, which may be due to the nerve entrapment in the muscles. Untreated spasticity can lead to contractures. Subsequently, pain, pain-induced insomnia, contractures, mobility impairment, potential for falls, and development of pressure ulcers due to tight muscles over bony prominences can impact quality of life.Bedside interventions such as avoiding inactivity and utilizing warm pool therapy may be helpful. Our findings support Boyraz et al.  that colMobility impairments leading to possible falls are a genuine concern. Even though risk of falls is an obvious issue, fall risk assessments are not routinely employed in an outpatient clinical practice. Since it is clear that an inherent risk for falls is present in this population, routine formal assessment of this risk should be done so that clinicians can assess patients status and their environment to minimize this hazard.The experience of spasticity is a quality of life issue, as its effects are pervasive in all domains of life. Therefore, clinicians must be cognizant of the consequences of this experience and mobilize appropriate resources based on individual needs. Individuals not only need medical intervention but also may require psychological counseling and strong spiritual connections to find an acceptable quality of life.Spasticity is a consequence of neuromuscular disorders, which affects quality of life in those who experience this phenomenon. Confusion regarding spasticity and related phenomenon in clinical practice warrants a pragmatic approach to this issue. Similar terminologies for hypertonia must be evaluated in the context of pathophysiology, impact on functioning, symptom consequences, and treatment options. The goals of rehabilitation are to improve function, comfort, and ADLs, decrease caregiver burden, and prevent pressure ulcers. Clinicians working in the field of rehabilitation strive to help people make their own lives work. This requires careful assessment and intervention of spasticity related symptoms.


One of the generally recognized factors contributing to the initiation and maintenance of atrial fibrillation (AF) is structural remodeling of the myocardium that affects both atrial cardiomyocytes as well as interstitium. The goal of this study was to characterize morphologically and functionally interstitium of atria in patients with AF or in sinus rhythm (SR) who were indicated to heart surgery. Patient population consisted of 46 subjects  undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atria were examined using immunohistochemistry to visualize and quantify collagen I, collagen III, elastin, desmin, smooth muscle actin, endothelium and Vascular Endothelial Growth Factor (VEGF). The content of interstitial elastin, collagen I, and collagen III in atrial tissue was similar in AF and SR groups. However, the right atrium was more than twofold more abundant in elastin as compared with the left atrium and similar difference was found for collagen I and III. The right atrium showed also higher VEGF expression and lower microvascular density as compared to the left atrium. No significant changes in atrial extracellular matrix fiber content, microvascular density and angiogenic signaling, attributable to AF, were found in this cohort of patients with structural heart disease. This finding suggests that interstitial fibrosis and other morphological changes in atrial tissue are rather linked to structural heart disease than to AF per se. Significant regional differences in interstitial structure between right and left atrium is a novel observation that deserves further investigation. Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in human . Rarely,It is generally accepted that a characteristic hallmark of structural remodeling and an important morphological substrate of AF is interstitial fibrosis. Morphologically, fibrosis is defined as an increased fraction of extracellular matrix, in particular collagen fibers . In addiThe objective of the present study was to perform a comprehensive analysis of atrial morphology with the aim to compare tissue samples from the left and right atrium harvested during open-heart surgery in patients with sinus rhythm (SR) or AF.The study group consisted of 46 patients (19 with long-term persistent AF and 27 in SR) who underwent cardiac surgery at the Institute for Clinical and Experimental Medicine in Prague. In both AF and SR groups, there were patients who underwent coronary artery bypass surgery or valve surgery . The stuTissue samples were obtained during open-heart surgery. A piece of atrial tissue of a maximum size of 5*5 mm was excised as a transverse section from the right appendage, the left free atrial wall and from the left appendage. Samples were immediately fixed with 4% formaldehyde. No complication occurred as a consequence of tissue sampling.Harvested atrial samples were embedded into paraffin and cut to 7μm thick tissue sections. Sections were subsequently dewaxed and rehydrated. Deparaffinized tissue sections were histologically examined using routine hematoxylin-eosin staining. Immunohistochemistry was used to visualize collagen I, collagen III, elastin, desmin, smooth muscle actin and VEGF in these samples . Three-sTo detect capillaries within the atrial tissue, we used biotinylated Ulex europaeus agglutinin I  that was applied (1:200) overnight at 4°C. Visualization of lectin binding was performed using the Vectastain Elite ABC kit standard .For assessment of desmin expression in pericytes and other cells, we used immunofluorescence staining with the use of primary monoclonal mouse anti-human desmin 1:100 in 1% goat serum in PBS and secondary anti-mouse Alexa Fluor 532  1:500 in 5% goat serum in PBS antibodies.To detect pericytes for microvessel pericyte coverage index assessment, we used monoclonal mouse anti-human smooth muscle actin antibody and biotinylated Ulex europaeus agglutinin I  diluted 1:200 in 1% goat serum in PBS. Streptavidin Alexa Fluor 488  1:100 and anti-mouse Alexa Fluor 532  1:500 in 5% goat serum in PBS were used in the next step. The nuclei were stained with DAPI 1:1000. Negative controls were used for all experiments.To quantify collagen I, collagen III and elastin volume fraction, we used the program Image J 1.44p . Images for quantification were collected by systematic uniform random sampling of tissue sections using the 40x dry objective of a Leica DMLB microscope . From each sample of atrial myocardium, 10 images from a single section were recorded. Individual recordings were separated from each other by 1 image frame. Images were converted to an 8-bit grey scale format and the threshold was set above the background staining intensity. Immunolabelled areas were automatically detected and area fraction was calculated for collagen I, collagen III and elastin. Only endomysial collagen and elastin fibers were quantified in this analysis. Perimysial connective tissue separating sheets of myocardial cells was excluded from quantitation as well as epicardial and endocardial connective tissue.To quantify microvascular density Ulex europaeus agglutinin I staining was used. Measurements were made using Image J 1.44p . Images for quantification were collected as described above and microvascular density was calculated as the number of capillaries per area unit.VEGF expression was analyzed semiquantitatively. Microphotography and image sampling was performed as described above. We evaluated the intensity of positive cardiomyocytes, adipocytes, mesothelial cells and capillaries. The intensity score consisted of four grades (0–3), with 0 representing no staining and 3 denoting the maximum staining effect.To quantify microvessel pericyte coverage index, we used immunofluorescence staining and analyzed microvessel pericyte coverage of capillaries in the atrial myocardium. Pericytes were identified as cells immunoreactive for smooth muscle actin and characterized as elongated cells surrounding capillaries. Capillaries were positive for Ulex europaeus agglutinin I and marked in green. Random areas were photographed using a Confocal Laser Scanning Biological Microscope Fluoview FV1000 Spectral Type (Olympus) equipped with a 40× oil immersion objective and analyzed by Olympus Fluoview 10-ASW 3.1 software. The percentage of capillaries with pericyte coverage was counted.Those who performed image analysis and scoring of immunohistochemical labeling were blinded to patient characteristics.P < 0.05 was considered significant.The values are expressed as a mean±SD. Comparison between both groups was performed using a non-parametric test—Mann–Whitney U test. A value of Clinical characteristics of the patient population are listed in To compare the level of fibrosis in atrial tissue samples from patients with SR and AF, we focused first on collagen I in the atrial endomysium, using immunohistochemical detection. Variable amount of collagen I was found in samples from both patient groups . In sampElastin was detected in human atrial samples in variable amount . Some saVEGF immunoreactivity was discovered in all atrial tissue samples that were examined. We focused not only on the myocardium but also on endocardial and epicardial layer. In the epicardium, VEGF immunoreactivity was found in mesothelial cells and adipocytes as well as in cardiomyocytes and blood vessels, mainly capillaries . The expMicrovasculature was analyzed in tissue samples from the same patient groups as VEGF expression. Using UEA-lectin blood vessel endothelium was visualized in atrial myocardium ; microvaTo evaluate possible differences in activity of angiogenic process in atrial myocardium of patients with AF and in SR, microvessel pericyte coverage of capillaries in atrial tissue samples was analyzed. Expression of two most commonly used markers: desmin and smooth muscle actin was assessed. While desmin was immunopositive in cardiomyocytes, capillaries were devoid of desmin signal . On the This study that aimed at a comprehensive analysis of atrial interstitium in patients undergoing cardiac surgery for significant cardiovascular disease with and without previous history of AF provided results that can be summarized as follows: 1) despite the fact that subjects with AF had significantly larger atria and were older, no significant differences in the amount of collagen I and III, and of elastin were observed in their atrial interstitium in comparison with patients in SR group, 2) both patient groups also did not differ in expression of atrial myocardial VEGF or in microvascular density, 3) tissue content of elastin, collagen I and collagen III and VEGF expression in the right atrium were significantly higher than in samples obtained from the left atrium, and 4) microvascular density was greater in the left atrial myocardium compared to the right atrial myocardium.Despite a plethora of studies published in the past that focused on specific morphological features of human atria during AF, this paper presents a study based on bioptic samples from both left and right atria and compares two cardiac patient groups with and without long-term persistent AF. We could confirm that both atria are dilated in patients with AF, while there is no significant difference in the left ventricular parameters as reported also in other studies with similar patient groups , 12. TheIn addition, earlier studies that showed more significant morphological changes in atrial tissue of AF patients used different methodology for collagen detection and quantification , 14, 15.As shown by our data, the expression of VEGF can be regularly detected in atrial samples of patients regardless of their heart rhythm. Importantly, there was no significant difference in myocardial VEGF expression between patients with AF and SR. In this respect, the mere presence of VEGF suggests active angiogenesis or at least the effect on maintenance of vascular bed in the myocardium of patients with various heart pathologies. One study on biopsies from right atrial appendages of patients undergoing routine open heart surgery reported on an increased expression of VEGF in AF patients . HoweverIn line with similar VEGF expression in atria from patients with SR and AF in this study, we also found comparable microvascular density in atrial myocardium of both patient groups. Similar finding was reported in one above mentioned study. The authors discovered no difference in microvascular density in the right atrial appendage biopsies of patients undergoing open heart surgery both with and without AF . CapillaAnother novel observation of our study is anatomical variability both in VEGF expression by cardiomyocytes and microvascular density. Higher VEGF expression of right atrial cardiomyocytes could reflect a need for stronger angiogenic stimulation as cardiomyocytes are according to our data separated from each other by a higher amount of extracellular matrix fibers in endomysium that has less dense microvascular network. Another possibility how to further characterize myocardial vasculature is to determine pericyte coverage index of microvessels. Our findings demonstrate again similar level of microvessel pericyte coverage index in myocardia of patients regardless of heart rhythm. Microvessel pericyte coverage index found in our study is comparable with findings in normal rat hearts that have microvessel pericyte coverage index around 84% . AlthougThe study shares several limitations common to a histopathological approach that uses material obtained from living patients during surgery. Our patient groups were relatively small and this fact might have influenced our quantitative results. For obvious ethical reasons, bioptic samples can be only of a limited size and number, and can be safely harvested only from certain locations within the atrial wall. As our knowledge of myocardial architecture expands, it is becoming increasingly obvious that there is a high level of variability even within a single atrium . We analComprehensive analysis of bioptic samples of atrial tissue in a cohort of cardiac patients undergoing open heart surgery revealed that the interstitium has variable morphology, especially in terms of the amount and composition of extracellular matrix. However, we could not confirm a higher level of fibrosis specific for AF. This finding suggests that interstitial fibrosis and other morphological changes in atrial tissue are rather linked to structural heart disease than to AF per se. Whether such patient will develop AF, depends most probably on additional presence of triggers and modulating factors. In addition, we showed that differences in the degree of structural remodeling between left and right atrium may be more important for etiopathogenesis of AF. Regional variation in matrix fiber content, microvascular density and VEGF expression deserve further investigation.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.S3 TableTable shows the results of quantitative analysis of several morphological parameters as a comparison between samples from patients with atrial fibrillation (AF) or sinus rhythm (SR). Details of histomorphometry are described in Methods. The values are expressed as the mean±SD. Comparison between both groups was performed using a non-parametric test—Mann–Whitney U test. A value of P < 0.05 was considered significant.(DOC)Click here for additional data file.S4 TableTable shows the results of semiquantitative analysis of VEGF expression. Details of histomorphometry are described in Methods. Table shows the intensity of positive cardiomyocytes, fat cells, mesothelial cells and capillaries. The intensity score consisted of four grades (0–3), with 0 representing no staining and 3 denoting the maximum staining effect. The values are expressed as the mean±SD. Comparison between both groups was performed using a non-parametric test—Mann–Whitney U test. A value of P < 0.05 was considered significant. ND = not determined.(DOC)Click here for additional data file.


Magnetic resonance (MR) tagging analyzed by dedicated tracking algorithms allows very precise measurements of myocardial motion and characterization of regional myocardial function. No extensive data are available in literature. Our aim was to quantitatively assess for the regional myocardial contractility in thalassemia major (TM) patients and to correlate it with heart iron overload and global biventricular function.Seventy-four TM patients  enrolled in the MIOT  network underwent MR (1.5T). Three short-axis  tagged MR images were analyzed off-line using harmonic phase (HARP) methods (Diagnosoft software) and the circumferential shortening (Ecc) was evaluated for all the 16 myocardial segments. Four main circumferential regions  were defined. The same axes were acquired by a T2* GRE multiecho technique to assess myocardial iron overload (MIO). Biventricular function parameters were quantitatively evaluated by cine images.Segmental ECC values ranged from -9.66 ± 4.17%  to 13.36 ± 4.57% (mid-anterior segment). No significant circumferential variability was de-tected. Compared with previous studied healthy subjects, TM patients showed strain values sig-nificantly lower in all the circumferential regions at each level  . This study was also supported by: "Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 e s.m.i., ricerca.


In left ventricular heart failure, blood will congest backwards to the pulmonary circulation and result in an increased pulmonary vascular resistance. If the increase in pressure result in impaired gas exchange due to pulmonary oedema, the pulmonary blood will redistribute to better ventilated areas in order to maintain adequate gas exchange. This mi: Fifteen patients with heart failure and 10 healthy volunteers underwent cardiac MRI at 1.5T. Flow measurements were acquired in the pulmonary trunk and all pulmonary veins. The PBVV was calculated by integrating the flow in all vessels leading to and from the pulmonary circulation. The PBVV was indexed to right ventricular stroke volume (PBVV/SV). Patients underwent a 6-minute walk test (6MWT) as an independent measure of functional capacity.Left ventricular ejection fraction (LVEF) in patients with heart failure and healthy controls were 27 ± 6 and 60 ± 3%, respectively p < 0.001). Patients had a significantly higher PBVV/SV compared to controls (58 ± 12% vs 40 ± 5%, p < 0.001, Figure . PatientPatients with heart failure had a higher PBVV/SV compared to healthy controls. This can be explained by a pulmonary circulatory response, either active or passive, to the failing left ventricle. However, the lack of correlation between PBVV/SV and LVEF, AVPD, or 6MWT suggests an active process in order to maintain an adequate gas exchange in the lungs. Therefore, we propose that PBVV/SV may be a measure of the pulmonary circulatory involvement caused by heart failure.Swedish Research Council, Swedish Heart and Lung Foundation, Medical Faculty at Lund University, Region of Scania.


Different from other indicators of cardiac function, such as ejection fraction and transmitral early diastolic velocity, myocardial strain is promising to capture subtle alterations that result from early diseases of the myocardium. In order to extract the left ventricle (LV) myocardial strain and strain rate from cardiac cine-MRI, a modified hierarchical transformation model was proposed.i.e., the normal volunteer and a diabetic patient) to evaluate their respective function.A hierarchical transformation model including the global and local LV deformations was employed to analyze the strain and strain rate of the left ventricle by cine-MRI image registration. The endocardial and epicardial contour information was introduced to enhance the registration accuracy by combining the original hierarchical algorithm with an Iterative Closest Points using Invariant Features algorithm. The hierarchical model was validated by a normal volunteer first and then applied to two clinical cases (Based on the two clinical cases, by comparing the displacement fields of two selected landmarks in the normal volunteer, the proposed method showed a better performance than the original or unmodified model. Meanwhile, the comparison of the radial strain between the volunteer and patient demonstrated their apparent functional difference.The present method could be used to estimate the LV myocardial strain and strain rate during a cardiac cycle and thus to quantify the analysis of the LV motion function. Diabetes mellitus, which can cause chronic, progressive disorders of multiple organs or systems, increases rapidly in recent years. As one of the major complications of diabetes mellitus, diabetic cardiomyopathy is defined as the left ventricle (LV) dysfunction independent of the coronary artery disease and hypertension . In the etc. are always clinically measured to evaluate the cardiac function, but these indicators do not directly reflect information of complex regional myocardial motion and sometimes are insensitive to subtle cardiac functional changes. In this regard, different from the above indicators, myocardial strain  holds the promise of capturing the subtle alterations that result from early diseases of the myocardium [Echocardiography, as a reference standard to estimate the cardiac function, is frequently used for the diagnosis of diabetic cardiomyopathy. Especially in recent years, Tissue Doppler Imaging (TDI) echocardiography has been considered as a new sensitive technique for the evaluation of diastolic function, based on the measurement of wall motion velocities . Thereinocardium .Myocardial strain can be measured by a variety of noninvasive imaging tests, among which measurements based on echocardiography and cardiac magnetic resonance imaging (MRI) have been mostly adopted ,6. EchocIn this paper, we proposed a method to extract the LV myocardial strain and strain rate from cardiac cine-MRI in terms of its high soft-tissue contrast, and employed a nonrigid registration-based method, to calculate the myocardial strain directly from cine-MRI without additional imaging sequences such as tagging.et al. [The goal of image registration in cine-MRI sequences is to find an optimal transformation by correlating any point in any frame of a cardiac cycle to that in a reference frame (end-diastolic). This transformation maps a complete myocardial displacement field at any time during a cardiac cycle. In general, the LV myocardial motion is nonrigid so that a nonrigid hierarchical transformation model is employed for the estimation of LV myocardial deformation field over a cardiac cycle. The model has been introduced by Rueckert et al.  and usedet al. ,12. HereThe hierarchical transformation model, which describes both the global and local motions of the left ventricle ,12-14, cThe affine transformation is used to model global large translation, rotation, scaling, shearing, or their combinations instead of local small deformation. It can be written ask is the scaling factor, k, θ, Δx, and Δy are parameters to be optimized. Thus, the global deformation can be written aswhere FFD deforms an object by warping the whole mesh of all control points in which the object is embedded instead of warping the object directly. As it contains a number of desirable properties, such as good approximation, local control, smoothness, and computational efficiency, the B-spline FFD is widely used to model deformation. It is written as a tensor product of two standard cubic B-splines,i,j ϕdenotes a quadrilateral mesh with x n× y ncontrol points in equispaced δ, mB(u) and nB(v) are basis functions of the B-spline, which are expressed aswhere i,j ϕplays the role of parameters in the B-spline FFD transformation and global registration should be performed before the local registration. Finally, the combined transformation is expressed asIt is noted that T, which maximizes the match between the reference image A and the target image B. Here, for the sake of the simplicity, we use the sum of squared differences (SSD) as an image similarity criterion (cost function), which quantifies the image intensity difference, and it is written asIn essence, image registration is an optimization problem. Its aim is to find the optimal coordinate transformation N is the number of pixels in the image. To find the optimal transformation, we need to minimize the cost function. Here, an iterative gradient descent method is employed to find the optimal solution of the hierarchical model parameters. The gradient descent method, which has a linear convergence rate [where nce rate , takes sμ represents the parameter vector, g(kμ) is the derivative of the cost function evaluated in iteration k. k ais the gain factor, which can be simply set to a constant. It is noted that the coordinate after transformation may not be an integer, thus, a cubic spline interpolation is employed in the process of transforming the original discrete image into continuous image.where ICPC, corresponding to the potential energy of the corresponding contours.As we know, morphological and dynamic information of heart is complex. Cardiac MRI is easily to generate weak edges at the boundary where tissues have low contrast in gray. Especially, features of the images significantly change if a large deformation occurs. These factors can negatively affect the registration accuracy. To solve this problem, we combine a variant design of iterative closest point (ICP) algorithm with the local registration algorithm to introduce the endocardial/epicardial contour information. We augment the criterion (6) with an additional term iP, i = 1,2,3...}, and endocardial/epicardial contour point in the target image (any other frame) as the target point set {iQ, i = 1,2,3...}. i Qmoves with the mesh of control points in the B-spline FFD model. In the iteration k, the target point set is updated to ICP is an iterative descent procedure minimizing the distances between points in the target point set and their closest points in the source point set. Its goal is to find a rigid transformation that maximally aligns the two point sets . Here, eet al. [x1 y1) and (x2 y2) are their Cartesian coordinates, k1 and k2 are their curvatures [Regarding the method to determine the closest point set corresponding to the source point set, Sharp et al.  firstly et al. . Thus, wrvatures . Now we α1 and α2 are reciprocals of the difference between the maximal and minimal values of their post-multiply terms.where the first term is the squared Euclidean distance, the second is the squared distance in the feature space, ICP Cis defined as the sum of the distance (8) between the contour point sets {iQ} and {iq} asThus, the additional term and the cost function can be rewritten asλ is the weighting factor to adjust the impacts of images intensity difference and the distance between the corresponding endocardial/epicardial contours, and it can be increased appropriately in case of a large deformation to increase the contribution of ICPC.where ICP Cdoes not increase the computing load much, moreover, it can improve the calculation efficiency and avoid falling into a local minimum. We used Gradient Vector Flow (GVF) Snake algorithm for endocardial/epicardial contours extraction because it can effectively segment weak edges [etc.) for estimating cardiac function from cardiac MRI are based on segmentation of the endocardial and epicardial contours. Therefore, it is meaningful to introduce endocardial/epicardial contour information to improve the registration effects, if strain and strain rate are developed as common clinical indexes for estimating regional myocardial function.The addition of the term ak edges . As propak edges , one of The LV myocardial displacement field over a cardiac cycle can often be extracted by the following two methods: (1) minimizing the cost function between every frame and the first one in the image sequence, which is used as the reference frame , thus, tThe data of the LV short axis from a normal volunteer and a diabetic patient without clinical symptoms were acquired with a clinical 3.0 T MR scanner . The abnormal subject represented a LV diastolic dysfunction reflected by the LV volume-time curve but had a normal EF value (>50%). The values of acquisition parameters were: slice thickness = 6.0 mm, gap between slices = 1.5 mm, in-plane resolution = 1.25 mm × 1.92 mm, and Field of View (FOV) = 276 mm × 340 mm. The clinical data used in this study was approved by the internal review board, and informed written consent was obtained.The present algorithm is evaluated through two studies using clinical data.i.e., excluding endocardial/epicardial contour information) and by the modified method , respectively. Second, for reference displacement fields of the two mentioned landmarks (A & B), they are manually defined in all frames according to the experience of a clinician. The displacement curves obtained from the hierarchical transformation algorithm are compared with the reference values. The result is plotted in Figure In the first study, the proposed model is verified by calculating the displacements of two anatomical landmarks of LV myocardium during a cardiac cycle in a normal volunteer. The two landmarks are near the middle endocardium, and they locate at the large deformation position  of the difference between the results of the modified/original method and the reference values of the two landmarks are shown in Table In the second study, we calculate the average radial strain and strain rate of each segment of the LV myocardium to evaluate regional LV myocardial function, according to the American Heart Association (AHA) 17-segment model. The results are depicted in Figure From Figure Strain rate is computed as a derivative of the strain tensor and it is a measure of the rate of deformation. A negative strain rate means that the tissue segment becomes thinner, whereas a positive strain rate means that the segment becomes thicker. From Figure The purpose of this study is to apply the proposed method to estimate the LV myocardial strain and strain rate over a cardiac cycle based on conventional 2D cardiac cine-MRI, and further to evaluate its efficiency. This method includes both small and large deformations of the LV myocardium, and it provides a high degree of flexibility to describe the global and local LV myocardial deformations. Furthermore, we studied the modified method's performance when it was applied in the clinical cases of a normal volunteer and a diabetic patient.In the algorithm, we added an additional term to the cost function to constrain the FFD transformation correctly. This idea stems from , in whicThe method has some advantages. First, it is entirely a post-processing method and needs no assumption about the physical properties of the tissues. Second, it computes the myocardial displacement field, and makes use of the whole myocardial information instead of just the myocardial edges information. Meanwhile, it provides the deformation information of the whole LV myocardium over a cardiac cycle. This is quite different from some other strain analysis systems that use boundary tracking methods to extract myocardial deformation . Third, Indeed, there are limits for the present model. The original clinical data are transverse-sectional images, so that motion and deformation were only characterized in 2D, therefore, the LV myocardial motion in the long axis direction was not taken into consideration. Moreover, the original hierarchical transformation model will produce a large error if the twisting is neglected under the large deformation; for the present modified hierarchical transformation model, it works effectively with the apparent curvature variation for the circumferential adjustment. Further work will focus on the assessment of the algorithm for the detection and diagnosis of early diabetic cardiomyopathy.In this paper, we proposed a modified nonrigid image registration method, which combines affine transformation with B-spline FFD transformation and includes the endocardial/epicardial contour information for registration amendment. The application in the clinical cases of a normal volunteer and a diabetic patient validated that the proposed method is effective to estimate the regional LV myocardial motion and function during a cardiac cycle based on 2D cardiac cine-MRI. Meanwhile, it demonstrated that the functional difference between the normal volunteer and the diabetic patient. The present method could be used as a promising approach for early detection of diabetic cardiomyopathy in diabetic patients with LV diastolic dysfunction.The authors declare that they have no competing interests.YG, QC and ZL proposed the method, and implemented the analysis, SZ and SJ provided the clinical imaging data; YG has drafted the manuscript, and QC is responsible for revising it critically; ZL has given final approval of the version and agree to be accountable for all aspects of the work. All authors read and approved the final manuscript.YG: M.E., Biomechanics Laboratory, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China; QC: Ph.D., Associate Professor, Biomechanics Laboratory, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China; SZ: Ph.D., Zhongda Hospital, Southeast University, Nanjing, China; SJ: Ph.D., Full Professor, Zhongda Hospital, Southeast University, Nanjing, China; ZL: Ph.D, Full Professor, Principal Investigator, Biomechanics Laboratory, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.


Imaging of the isolated heart eliminates respiratory motion and, if conducted on arrested hearts, cardiac pulsation. This serves as an important intermediate step for basic and translational studies. However, investigating the micro-structural basis of cardiac deformation in the same heart requires observations in different deformation states.Diffusion tensor magnetic resonance imaging (MRI) reveals valuable insights into tissue histo-anatomy and microstructure, and has steadily gained traction in the cardiac community. Its wider use in small animal cardiac imaging T1, T2 or LV wall thickness over a 170 min period. In contracture, we observed a significant reduction in mean fractional anisotropy from 0.32 ± 0.02 to 0.28 ± 0.02, as well as a significant rightward shift in helix angles with a decrease in the proportion of left-handed fibres, as referring to the locally prevailing cell orientation in the heart, from 24.9% to 23.3%, and an increase in the proportion of right-handed fibres from 25.5% to 28.4%. LV overload, in contrast, gave rise to a decrease in the proportion of left-handed fibres from 24.9% to 21.4% and an increase in the proportion of right-handed fibres from 25.5% to 26.0%. The modified perfusion and coil setup offers better performance and control over cardiac contraction states.Here, we illustrate the imaging of isolated rat hearts in three mechanical states mimicking diastole (cardioplegic arrest), left-ventricular (LV) volume overload , and peak systole (lithium-induced contracture). An optimised MRI-compatible Langendorff perfusion setup with the radio-frequency (RF) coil integrated into the wet chamber was developed for use in a 9.4T horizontal bore scanner. Signal-to-noise ratio improved significantly, by 75% compared to a previous design with external RF coil, and stability tests showed no significant changes in mean ex vivo rat hearts in slack state and contracture. As a model-free method, DSI augmented the measurements of water diffusion by also informing on multiple intra-voxel diffusion orientations and non-Gaussian diffusion. This enabled us to identify the transition from right- to left-handed fibres from the subendocardium to the subepicardium, as well as voxels in apical regions that were traversed by multiple fibres. We observed that both the mean generalised fractional anisotropy and mean kurtosis were lower in hearts in contracture compared to the slack state, by 23% and 9.3%, respectively. While its heavy acquisition burden currently limits the application of DSI in vivo, ongoing work in acceleration techniques may enable its use in live animals and patients. This would provide access to the as yet unexplored dimension of non-Gaussian diffusion that could serve as a highly sensitive marker of cardiac micro-structural integrity.We subsequently performed high-resolution diffusion spectrum imaging (DSI) and 3D whole heart fibre tracking in fixed  Detailed characterisation of three-dimensional (3D) cardiac histo-architecture, and its dynamic alteration during the contractile cycle, offers great potential for new insights into the mechanics of cardiac contraction. Most studies of myocardial microstructure have been conducted on fixed samples, using tissue-destructive techniques such as serial histology sectioning. In contrast, diffusion magnetic resonance imaging (MRI) is a non-invasive tool that enables determination of 3D morphological features in the intact organ .D, and the degree of diffusion weighting, described by the b-value , which may serve as a marker of tissue integrity after acute myocardial infarction . DiffusiWhile the single tensor model in DTI has been widely used as an efficient approach for investigating diffusion, Brownian motion of water in tissues is a more complicated process, in no small part due to the presence of multiple populations of cell types and orientations in each imaging voxel. A number of methods have been developed to better reflect multiple fibre populations within a voxel. These include multi-tensor fitting , Q-ball P with a non-Gaussian distribution. If for example, diffusing spins encounter an impermeable restriction during a finite diffusion time, Δ, then their measured or apparent diffusion will underestimate their true diffusivity. The cumulant expansion is a useful framework that expresses the magnitude of the diffusion-weighted signal as a power series of the b-value   on the other hand, enables direct reconstruction of on (PDF) . In contorientation distribution function, which describes its orientation with no prescribed limitation on the number of dominant directions. Likewise, the shape of the PDF can be described by parameters such as the probability at zero distribution, the full-width-half-maximum and its kurtosis  characterise the microstructure in rat hearts in multiple (here three) deformation states using diffusion MRI, (ii) demonstrate how specialised hardware can improve the sensitivity of measurements and support more physiological conditions and (iii) show how a more comprehensive description of the diffusion profile expands our ability to characterise the microstructural properties of the heart.filling factor, and therefore the SNR. Further optimisation to the previous design include (i) improved temperature control to allow for experiments at body temperature, (ii) constant flow perfusion, and (iii) integration of a pressure-sensing balloon in the left ventricle (LV) cavity to assess and/or control the mechanical state of the heart. DTI experiments were performed to characterise cardiac microstructure in multiple mechanical states in the same heart. SNR, T1 and T2 were measured to quantify the utility of the integrated RF coil and assess sample stability. Subsequently, samples were fixed in slack or contractured states and scanned with isotropic 3D DSI to additionally investigate non-Gaussian diffusion changes characteristic of the different mechanical states.Refinement of the RF coil technology can improve the SNR of the MRI experiments, leading to significant differences in the accuracy and precision of the measured DTI parameters . Here, w22.12.1.1−1, rise time = 130 μs, and inner diameter = 60 mm). A dedicated fixed tune-and-match birdcage coil  was used for transmit/receive in the perfused heart experiments. For 3D DSI of ex vivo fixed hearts, a different transmit/receive birdcage coil was used , where tune-and-match were adjusted to each sample.All imaging was performed using a horizontal 9.4T (400 MHz) MRI system , bore size = 210 mm, a VNMRS Direct Drive console, and a shielded gradient system , the heart was cardioplegically arrested using a modified high-K+ Tyrode solution . All solutions were titrated to pH 7.4. A balloon was inserted into the LV cavity via an incision in the left atrium and through the atrio-ventricular valve. Contracture was induced in four hearts by switching the perfusate to Na+-free Li+-Tyrode solution .All animal work was conducted in accordance with the UK Home Office Guidance on the Operation of Animals (Scientific Procedures) Act of 1986, and was approved by the University of Oxford's ethical review board. Hearts were excised from seven female Sprague–Dawley rats (body weight = 256 ± 13 g) after cervical dislocation, and connected to the perfusion setup via swift cannulation of the aorta for coronary perfusion in Langendorff mode. An incision was made into the pulmonary artery wall distal to the right ventricular outflow valve to prevent intra-ventricular fluid accumulation. After the initial wash using normal Tyrode solution . For comparison, two additional hearts were excised and fixed in their cardioplegically arrested slack state via coronary perfusion with Karnovsky's fixative . The four fixed hearts were stored in fixative for at least 24 h at 4 °C, rinsed in iso-osmotic cacodylate buffer and embedded in iso-osmotic 2% low-temperature melting agar in 20 mm glass tubes.2.32.3.1N = 3) by measuring stability of T1 and T2 over a period of 170 min. The time delay between excision and the start of imaging was about 35 min. During the imaging period, myocardial T1 and T2 values and LV wall thickness were measured 10 times in 17 min cycles. T1 was assessed using a 2D multi-slice spoiled gradient echo sequence with inversion recovery: repetition time (TR) = 5 ms, echo time (TE) = 1.3 ms, 40 images with inversion times ranging from 80 to 6320 ms, flip angle = 8°, field-of-view (FOV) = 20 × 20 mm, matrix = 128 × 128, slice thickness = 1 mm, slices = 3, averages = 2. T2 was measured using a 2D multi-slice multi-echo spin echo sequence: TR = 2.5 s, 4.6 ≤ TE ≤ 73.3 ms, echo train length = 16, FOV = 20 × 20 mm, matrix = 128 × 128, slice thickness = 1 mm, slices = 5, averages = 2. T1 and T2 values were calculated on a voxel-by-voxel basis by applying a mono-exponential fit to the magnitude images using purpose-built software written in IDL . The myocardium was then manually segmented at each time point and mean values computed across the myocardium. The LV wall thickness was measured at two locations in a mid-ventricular slice from the T2 experiments using VnmrJ 3.2 . A two-sided, paired t-test was used to compare the parameters from the first and last time points. P ≤ 0.05 was used throughout the study to indicate a significant difference between means.Potential progression of myocardial oedema over time was investigated in three rat hearts  in the background. SNR maps were then obtained in the manually segmented myocardium by dividing the measured signal by the noise in each respective slice. Four datasets from a previous study using an external resonator (versus 21 °C in the previous study), and VP and VC are the voxel sizes in the previous and current experiments, respectively  were scanned using a diffusion-weighted multi-shot fast spin echo sequence. Images were acquired in the short-axis orientation of the heart in 13 contiguous slices covering the heart from apex to mitral valve using the following parameters: TR/TEeff = 1000/15 ms, echo train length = 8 , FOV = 20 × 20 mm, matrix = 128 × 128, in-plane resolution = (156 μm)2, slice thickness = 1 mm, averages = 12, acquisition time = 35 min per state. Unipolar diffusion sensitizing gradients were used with maximum diffusion gradient strength, Gmax = 310 mT m−1, gradient duration, δ = 2.5 ms, separation time, Δ = 9.6 ms, and maximum b-value, bmax = 508 s mm−2 including contribution from imaging gradients and cross-terms. Ten non-collinear gradient directions were used . The balloon was then inflated to a pressure of 70 mmHg (volume loading). Finally, the balloon was deflated, and ventricular contracture was induced by switching the perfusate to Na2.4.3υ1, υ2, υ3) and corresponding eigenvalues . From these, maps of FA and ADC were calculated using established methods  and (b) the circumferential-radial  plane. For that purpose, the long axis of the LV was determined in each mechanical state by manually selecting the centre of the LV cavity in several slices. The long axis was then calculated by linear regression of these points, and the chamber–horizontal plane defined as perpendicular to this axis. Helix angles were defined as negative and positive for left- and right-handed helical orientations, respectively. The voxels were then binned according to the measured helix angle into left-handed fibres (LHF: α ≤ −30°), circumferential fibres (CF: −30° < α < 30°) and right-handed fibres (RHF: α ≥ 30°). The papillary muscles and trabeculae were excluded from the analysis. The changes in the partition of fibres between the three mechanical states were analysed using a 3 × 3 chi-square test.Diffusion tensors were calculated on a voxel-by-voxel basis via a weighted linear least-squares fitting method, using in-house software developed in IDL. Tensors were diagonalised to obtain the eigenvectors  k-space . Unipola phantom .2.5.2A 3D Fourier transform was applied to the signal in a voxel-by-voxel manner in q-space to generate the PDF Equation . Maps of33.13.1.1T1, T2 or LV wall thickness were detected. The mean myocardial T1 values were 2.03 ± 0.13 s (t = 0) and 2.16 ± 0.01 s . The mean myocardial T2 values were 39.4 ± 6.6 ms (t = 0) and 38.8 ± 5.3 ms . LV wall thickness values were 1.37 ± 0.02 mm (t = 0) and 1.39 ± 0.04 mm .The three hearts scanned in the initial control experiments showed little sign of gross anatomical change over the nearly three-hour period of investigation, and no significant changes in the mean 3.1.20 images . Representative images obtained with either setup are shown in The RF coil filling factor for our configuration compared favourably to that from the previous study (0.25 vs 0.047). This contributed to a 75% increase in mean SNR in the B3.2Images and DTI parameter maps obtained from the 3-state protocol are shown in P = 0.001), but not in ADC (P = 0.46). The post-hoc Tukey test found significant differences in FA between slack state and contracture  and between the volume overload and contracture . None of the eigenvalues showed statistically significant changes between the three states (P > 0.3). On the other hand, the changes in the ratios λ1/λ2 and λ2/λ3 were statistically significant . The post-hoc Tukey test showed significant differences in λ1/λ2 between the volume overload and contracture  and in λ2/λ3 between slack state and contracture  and between the volume overload and contracture .The mean and standard deviation of the DTI measurements over the whole myocardium are listed in P < 10−4).The changes in helix angles between the three mechanical states are shown in 3.3By progressively enlarging the ROIs used for seeding tracts, we observed a shift in fibre orientation from the almost longitudinal fibres of the trabeculae, through the right helical fibres of the subendocardium, circumferential fibres of the mid-myocardium and left helical fibres of the subepicardium . This prTracts seeded in single voxel radius ROIs in the septal and lateral LV walls further illustrate the transition between left helical fibres with negative helix angles in the subepicardium to right helical fibres with positive helix angles in the subendocardium . InspectComparison of DSI parameters over the whole heart reveals a number of striking differences . Relativ44.1The aim of the study was to develop and test an optimised MRI-compatible Langendorff perfusion setup for examination of live isolated rat hearts. To this end, we first integrated the RF coil into the perfusion chamber around the heart, thus improving the coil filling factor and resultant SNR. Considering only the increased filling factor, one would expect an improved transmit efficiency or receive sensitivity of t hearts . This cot hearts  and prott hearts .The insertion of a balloon in the LV provided improved control over cardiac contraction. The general approach was similar to Balloon insertion increased preparation time from ∼15 min to ∼35 min to the start of MRI acquisition. However, there were no signs of progressive oedema or other gross anatomical changes during the study period of nearly three hours. We attribute this to the use of body temperature and albumin-enriched buffer, which provided more physiological experimental conditions. Also, we have prevoiously shown that the largest step-change in cardiac tissue volume occurs very soon after cardiac excision, prior to the earliest time points at which MRI data can be obtained even if no balloon is inserted . This is4.22 blurring. The use of fast spin echo acquisition was robust against susceptibility artifacts , which have been shown to contribute to ventricular wall deformation during cardiac contraction . This wiin vivo vary widely, largely stemming from the different acquisition methods used which result in dissimilar sensitivities to motion. Potential factors leading to such variation include the choice of MRI pulse sequence, motion compensation of the diffusion gradients, and cardiac and respiratory gating, if used. As methods in mitigating and compensating for motion continue to improve, imaging of the isolated live heart can serve as a useful benchmark for the establishment of reference values, and be used for validating new methods in the absence of motion, prior to in vivo application. At the same time, it is important to recognize the contribution of partial volume effects, which manifest ubiquitously given the large voxel sizes with respect to the cardiac microstructure. An informed assessment of the limitations of the models used to fit the data is thus needed. For instance, in regions containing multiple fibres, the tensor model leads to ambiguity in the origin of FA changes  the diffusion tractography performed here is a simplification that does not reflect the complex branching patterns that occur between cardiomyocytes that are arranged in complex 3D structural domains, including sheets. Unlike histology, DSI can be used to study the intact cardiac architecture isotropically in 3D without distorting tissue and in a non-destructive manner. However, as with many other forms of high-resolution ex vivo imaging, it involves prior chemical fixation, which gives rise to changes in tissue geometry, membrane permeability, and ADC , volume overload (simulating increased venous return), and contracture (mimicking peak systole). Besides improving SNR, and thereby precision of DTI measures, the optimised setup provided better control over experimental parameters including the mechanical state, temperature, perfusate-tissue water balance, and allowed for physiological monitoring. Differences in non-Gaussian diffusion and tractography between slack and contractured hearts were identified using DSI, which also highlighted the presence of apical voxels that contain multiple fibre tracts. DSI is a versatile method that augments our ability to investigate water diffusion in the intact organ. It provides information on Gaussian and non-Gaussian diffusion for the characterisation of changes to tissue microstructure, including complex tissue morphometry and locally prevailing cell orientation, during cardiac deformation.Beyond describing differences between diffusion parametric maps, much work remains to further develop and validate biophysical models of diffusion that accurately represent the tissue micro-architecture. DSI, with its model-free approach, is well placed to serve as a benchmark for the development of such models, as well as a reference for validation of novel acquisition and post-processing methods. Further advances in acceleration techniques, including compressed sensing, may broaden the application of DSI in the heart. We anticipate that the next phase of development in imaging of freely beating isolated hearts will facilitate a more comprehensive characterisation of cardiac histo-anatomy throughout the cardiac cycle, and open up opportunities for translating basic science research and development to clinical application.Please see also related communications in this issue by


A 64-year-old Japanese man was referred to our hospital because of palpitation. An electrocardiogram revealed first-degree atrioventricular block without ST-T change. An echocardiography showed structural abnormality into the left ventricular outflow tract (LVOT), mitral valve leaflet cleft without mitral regurgitation, and single papillary muscle (loss of posterior papillary muscle) Figs. , 2. A stAMVT is a rare congenital cardiac malformation. The age of AMVT diagnosis ranged from newborns to 77 years . It was An echocardiography can be considered the gold standard modality for the diagnosis of AMVT with other cardiac abnormality.Although single papillary muscle usually combined the parachute mitral valve, the parachute mitral valve was not observed in this case. The majority of patients with AMVT have no symptoms, such as chest pain, palpitation, and syncope –7. Howev


It is still controversy in thalassemia major (TM) if Cardiovascular Magnetic Resonance (CMR) T2* screening should be initiated before the 10 years. To answer this question, we studied retrospectively the prevalence of cardiac iron and function and myocardial fibrosis by CMR in a consistent cohort of TM patients younger than 10 years.From the 2171 patients enrolled in the MIOT  network, we retrospectively selected the 35 TM patients aged less than 10 years who had undergone at least one MRI scan. Myocardial iron overload (MIO) was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated in a standard way by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired.Patients' age ranged from 4.2 to 9.7 years. All MRI scans were performed without sedation. Nine patients (25.7%) showed no myocardial iron overload (MIO), 22 patients (62.9%) showed an heterogeneous MIO with a T2* global value ≥ 20 ms; 2 patients (5.7%) showed an heterogeneous MIO and a T2* global value < 20 ms and 2 patients (5.7%) had a homogeneous MIO Figure . BiventrThe first cardiac T2* assessment should be performed as early as possible without sedation and it is mandatory whenever poor compliance is suspected or if chelation has been started late.The MIOT project receives "no-profit support" from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.). This study was also supported by: "Ministero della Salute, fondi ex art. 12 D.Lgs. 502/92 e s.m.i., ricerca sanitaria finalizzata anno 2006" and "Fondazione L. Giambrone".


Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations.Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller–Trumbore and Floyd–Warshall algorithms. IPM’s were reconstructed from the BSP’s.Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively.The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP’s.The online version of this article (doi:10.1186/s12967-016-0902-0) contains supplementary material, which is available to authorized users. Inverse potential mapping (IPM) and simulations of cardiac activation are promising computational techniques for non-invasive assessment of rhythm disorders , 2. ReceIn general, IPM requires a  mesh representing the thoracic and cardiac volumes to reconstruct cardiac activation sequences from body surface potentials (BSP). Similarly, realistic simulations demand for a patient-specific mesh, incorporating functional information about tissue characteristics such as electrical conductivity, mechanical deformation and fiber orientation , 4, 7. IAlthough the currently available models are useful, they are very time consuming , or too In addition, none of the currently available methods provide an integrated whole-heart  mesh, incorporating both the atria and ventricles. This limits a comprehensive and integrated study of whole-heart electrical interaction.This article proposes a comprehensive finite element model based whole-heart computational workflow suitable for IPM and efficient personalized simulations. The clinical feasibility of reconstructing IPM was explored using BSP’s of healthy volunteers and patients with premature ventricular contractions (PVC’s).Subsequently, the simulation features were explored by generating activation maps (isochrones) in different models of human hearts, both normal and with structural heart disease.The computational workflow for whole-heart electrical assessment consists of four steps Fig. . These sThree healthy volunteers and eight patients with symptomatic or therapy resistant premature ventricular contractions (PVC) participated in this investigation. The study complied with the declaration of Helsinki and received approval from the local ethical committee (METC Zuidwest Holland study number NL38156.098.11) and the institutional scientific board. Written informed consent was obtained from the volunteers.An MRI scout scan was performed to approximate the position of the heart with respect to the thorax. Subsequently, 62 (+3 limb) electrodes were applied to the subject’s torso, centralized over the heart. Body surface potentials (BSP) were acquired using a 65 channel ActiveTwo system . Once the acquisition was completed, the electrode locations were marked with MRI markers enabling accurate identification of the electrode positions.MRI studies were obtained on a 1.5 Tesla Aera scanner . Blackblood imaging was performed using a Half-Fourier Acquisition Single Shot Turbo Spin Echo (HASTE) pulse-sequence to acquire three perpendicular stacks . The scan provides coverage from the neck till lower abdomen.Images were acquired during free breathing using navigator gating (diaphragm) with 1 mm window. ECG gating was used to acquire views during the diastolic phase of the cardiac cycle. Typical imaging parameters were: a spatial resolution of 1.2 × 1.2 × 6 mm, TR/TE 744/42 ms and flip angle = 160°.A topologically correct description of the whole-heart anatomy was constructed using the different cardiac structures such as atrial and ventricular endocard and epicard, the inter-ventricular septum (IVS) and inter-atrial septum (IAS), and tricuspid and mitral valvular plane  denotes the outer surface of the left atrium. A unique color index describes the relation between the topological description and the colored planes that make up the segmentation.A shell is a set of patches denoting a closed surface. Example: shells.heart_outer = Shell  denote the whole outer surface of the heart.A hull is a three dimensional piece of tissue having uniform properties which may be irregularly shaped. A hull is bound by one or more shells where the first-mentioned shell is the outer surface of the hull and remaining shells are the inner surfaces of holes in the hull. Example: hulls.heart = Hull  denote the hart walls. In this example the heart is simplistically pictured as a closed volume with four holes, two for the atria and two for the ventricles.The three perpendicular stacks of MRI images were loaded in a custom developed software tool. Subsequently, the pre-defined anatomical and electrical components were segmented. The extra-cardiac thoracic volumes (lungs and thorax) were assigned conductivity values (Σ) described in the literature; lungs (0.04 S/m) and thorax (0.2 S/m) .To investigate the feasibility of incorporating tissue properties, two segmentations were created containing pre-defined regions of edema (speed 0.2 m/s and Σ 0.0325 S/m) and scar tissue (speed 0 m/s and Σ 0 S/m) respectively.The software tool was used to generate a script containing the geometrical description of the topologically correct segmentation result. From this script input a high quality 2D/3D mesh can be instantly generated. This mesh is compound, i.e. it is divided in labeled sub-meshes conforming organ boundaries, and suitable for computational use e.g. sub-volume properties and boundary conditions. The script generated by the segmentation tool was used as input to the GMSH mesh generator to construct the computational mesh .The IPM’s were reconstructed by multiplication of the BSP’s with derived .Simulations were performed using a fixed conduction velocity model. In concordance with the literature, an effective conduction velocity of 0.6 m/s was defined for both atrial and ventricular myocardium . Based oThe simulations were performed (1) computing direct connections between all mesh nodes using the Möller–Trumbore algorithm  followedBaseline characteristics of the three volunteers and eight patients N = 11) are provided in Table 1 are proFor each individual, five different volumes were defined at the atrial level consisting of the left and right atrium, IAS and the mitral and tricuspid valvular planes. The ventricular volumes were defined as the left and right ventricle and IVS  was successfully simulated on all healthy computational meshes. The generated virtual isochrones maps depicted cardiac activation patterns in accordance with the literature Fig. : Video 2The simulations for computational meshes with structural abnormalities (edema and scar), were also completed successfully. The mesh with a pre-defined virtual edema region demonstrated a delayed activation pattern Fig. , whereasTo our knowledge, this is the first study to integrate and evaluate IPM and cardiac activation simulations within a clinically applicable whole-heart workflow. The proposed computational workflow provided accurate IPM reconstructions and enabled patient-specific simulations to be performed.The use of MRI enables visualization and incorporation of tissue-characteristics in computational meshes. In addition, an integrated IPM and simulation based approach facilitates a comprehensive assessment of arrhythmias and underlying substrate. These two factors significantly contribute towards the clinical applicability of this workflow and offer a unique environment for the development and evaluation of patient tailored therapeutic strategies.The IPM localized the origin of atrial activity to the anatomically known location of the sinus node , suggestThe ability to reconstruct atrial depolarization and repolarization can also contribute to novel clinical insights in the electrical substrate of complex supra-ventricular tachycardias such as left atrial flutter and atrial fibrillation.The simulations of sinus rhythm performed on the computational meshes generated reliable results when compared to measurements reported in the literature . SimulatThese observations illustrate the wide range of simulations which can be obtained utilizing this simulation model. This can be clinically relevant for patients presenting with arrhythmias with a history of a disease associated with fibrosis such as myocardial infarction and myocarditis.Although only a few pathologies involve the atria and ventricles simultaneously, a combined assessment remains relevant for a comprehensive study of atrio-ventricular electro-mechanical coupling and electrical interaction.The atrial contraction presents such an example. It has been reported that pressure modulation due to atrial contractions can remotely alter the electrical behavior and activation pattern of the ventricular myocytes , 17. A wThe simulations performed in this study used a standardized set of epicardial potentials recorded in a structurally normal human heart. Furthermore, the currently used simulation algorithm applied fixed conduction velocities for the cardiac volumes.However, the aim of the current study was to develop a clinically applicable and reliable method for isochrones generation. The evaluation of this algorithm could be successfully performed using one set  of epicardial potentials. The generated simulation results were accurate for all subjects when compared to previous descriptions in the literature . TherefoThe customized meshes were constructed to test the feasibility of incorporating tissue properties. The conductivity and speed values for edema and scar tissue were based on estimates. Although, this can be considered as a substantial limitation, the simulations with patient-specific geometries (incorporating scar and edema) demonstrated realistic results, and underline the feasibility of the simulation algorithm.A next step would be combining simulations with reconstructed IPM in order to non-invasively characterize tissue.Future research will focus on evaluating the IPM algorithm for patients undergoing catheter ablation for ectopic ventricular beats. The simulation algorithm will be further evaluated and optimized in patients with structural heart disease and arrhythmias. Furthermore, future work will perform comparison between simulations, reconstructed IPM and invasively acquired epicardial potentials to evaluate potential reconstruction errors related to patient specific differences in epicardial potentials.The proposed finite element model based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using IPM and simulations. The IPM algorithm can accurately reconstruct reliable cardiac activation sequences from BSP’s. The simulation model was able to incorporate patient-specific electrical parameters and rapidly perform whole-heart cardiac activation simulations. The use of MRI substantially contributes towards the clinical applicability.This workflow offers the prospect to improve patient selection and personalize therapeutic strategies for interventional electrophysiological procedures. Future studies should investigate the role of this innovative approach for analysis of complex atrial and ventricular arrhythmias.