FIELD

The present disclosure relates to systems, computer-readable media, and methods for assessing physiological condition of spinal intervertebral discs in a quantitative manner using magnetic resonance imaging (MRI) data. The systems, media, and methods described herein provide a simple, objective, continuous measurement of disc ‘health’ or degeneration/pathology using routinely acquired digital MRI sequences. More specifically, they provide a calculation of a value based on one or more ratios from signal-based measurements of spinal disc structures or regions, which can be obtained either through manual tracing or automated through programming of image analysis software.

DESCRIPTION OF THE RELATED ART

The intervertebral disc is a major focal point of research and clinical investigation into back pain problems and other common spinal disorders, such as disc herniation and spinal stenosis, which are associated with disc degeneration. While the majority of patients seeking care for back pain complaints, estimated at around 85%, cannot be given a precise pathoanatomical diagnosis, the disc has long been suspected as a culprit. This suspicion drives vast amounts of clinical imaging and spine surgery. In fact, “degenerative disc disease” is currently the leading diagnosis associated with spine fusion in North America (Rajaee S S, Bae H W, Kanim L E, Delamarter R B Spine 37:67-76; 2012). Yet, the role of disc degeneration in common painful spinal disorders remains controversial. One factor limiting research and current knowledge of the relation of the disc to the onset and prognosis of painful spinal disorders is the quality and validity of measurements of disc degeneration and pathology.

Most current research on disc degeneration based on MR imaging uses visually evaluated 2 to 6 point ordinal scales of various degenerative signs. Kellgren J H and Lawrence J S (Ann Rheum Dis 16:494-502; 1957) introduced an x-ray based 5-point grading scale of osteoarthritis, including osteophytes and joint narrowing among other findings. However, the lumbar spine was “omitted because of difficulties with reproduction.” Yet, osteophytes and disc narrowing became common elements of disc degeneration assessments used over subsequent decades, and disc bulging and signal loss were added later following the advent of MRI using T2 weighted images. These findings have been commonly included in numerous qualitative or visual assessments of disc degeneration, and have been considered individually or collectively through global disc degeneration scores. Schneiderman G, et al. (Spine 12:276-81; 1987) introduced a 4-point visual grading scale based on disc signal on MRI, which was then “validated” by comparison with discography scores on 36 patients. Approximately 15 years later, Pfirrmann C W and Resnick D (Radiology 219:368-374; 2001) created a gross 5-point ordinal scale for disc degeneration based on signal loss and heterogeneity and disc narrowing, which is currently widely used. The Pfirrmann scoring system has surprisingly high associations with age (an indicator of measurement validity), particularly in the upper lumbar discs, despite the grossness of the scale (shown in the validation section of this document). More recently, a “modified Pfirrmann” 8-point grading system was introduced, again based on disc signal and consideration of additional degrees of disc narrowing (Griffith J F, et al., Brit J Industr Med 32:E708-E712; 2007).

The most notable limitations of such qualitative rating systems of disc degeneration are lack of measurement precision and suboptimal measurement reliability. Other limitations include the frequent aggregation of different degenerative signs that may represent very different pathological or adaptive processes into global summary scores. For example, atrophic and proliferative changes as seen in disc narrowing and osteophytes of adjacent bone may have different determinants and differ in their clinical relevance, but have been combined into summary measures of disc degeneration (Sambrook P N, MacGregor A J, Spector T D. Arthritis Rheum 42:366-72; 1999). Such summary measures may dilute true associations that would be identified with specific measures.

Another significant challenge with most signal-based measures of disc degeneration is magnetic field heterogeneity, which influences signal and creates artifacts, particularly at the periphery of the field. Although the human brain is able to adjust visual assessment scoring to some extent to account for such variations due to signal strength within a sagittal image of a lumbar spine, for example, comparisons between scans and scanners are compromised. This problem has led some to adjust the signal of a particular structure or region of interest by an intra-body reference, such as adjacent cerebrospinal fluid (CSF), when using quantitative measurements (Battié M C, et al. Spine 20:2601-2612; 1995; Carragee E J, et al. Spine 34:2338-2345; 2009; Michopoulou S, et al. Acta Radiol 52:91-98; 2011). Visual assessments of one degenerative finding also can influence or bias the grading of other findings. For example, a narrowed disc may affect judgments of disc signal, bulging and osteophytosis, particularly when findings are marginal. In addition, all of the known qualitative grading systems use sagittal images, often the mid sagittal image, which samples a limited section of the disc.

Current quantitative disc degeneration measures using MRI data provide continuous or interval measurements, and are based largely on desiccation and loss of proteoglycans and collagens, but do not directly consider disc morphology and loss of structural integrity or annular disruption. When the signal on MRI T2-weighted sequence measures water concentration, the disc signal strength is theoretically an ideal measure of disc degeneration as indicated through desiccation. However, as mentioned above, unadjusted quantitative signal strength varies significantly between scans and scanners due to magnetic field inhomogeneity, individual anthropometrics and other factors. (Prott F J, et al. Radiother Oncol 37:221-224; 1995).

Antoniou J, et al. (Magn Reson Med 40:900-907; 1998) measured the content of proteoglycans, collagens and denatured collagens in the nucleus and annulus of 19 subjects (age range 19-79 years) and used T1 and T2 relaxation and magnetization transfer to “reflect . . . nucleus matrix composition of the disc” and its “structural integrity.” In addition, “the apparent diffusion coefficient along the anterior-to-posterior axis of the nucleus” was correlated with the proteoglycan content using standard Siemens quantitative MR packages and showed some associations with age and Thompson's morphological grade (Antoniou J, et al. Spine 31:1547-1554; 2006). In another study, Nguyen A M, et al. (J Bone Joint Surg Am 90:796-802; 2008) concluded that Tlrho relaxation time correlated with water content (r=0.53), glycosaminoglycan content and swelling pressure, and has potential as a quantitative biomarker of disc degeneration. Michopoulou (2011) applied texture analysis of medical images to quantification of lumbar disc degeneration from conventional T2 MR images. Such image-based quantification has similarities to an earlier method which counted signal differences between neighboring pixels and was associated with age similarly to obtain mean CSF-adjusted disc signal strengths. This earlier method considered the inhomogeneity and variation in magnetic field strength by adjusting the signal measures by the adjacent CSF signal, and while less than perfect, is clearly better than no adjustment (Videman, 2008).

NMR spectroscopy and high-resolution magnetic angle spinning (HR-MAS) techniques have been used to identify and measure disc biochemical substances, but do not directly measure disc matrix abnormalities and the measures also need to be adjusted for variation in magnetic field strength, as noted by a representative of NOCISCAN™. (Diagnostics, Data, Deformity. 7thAnnual Spine Technology Summit Oct. 23, 2013; Dallas). A 2011 article covered the main quantitative MR imaging measures in disc degeneration (Majumdar S, et al. J. Orthop Clin North Am 42:501-11; 2011).

Diffusion MRI and disc degeneration are less strongly associated than some of the earlier measures mentioned and diffusion MRI does not distinguish well between normal and degenerated discs (Niinimaki J, et al. Magn Reson Imaging 27:641-647; 2009). Furthermore, diffusion values are associated with biomechanical loading conditions. Diffusion imaging is also done with contrast agents, but these are unpractical and have not been shown to be clearly better than the other assessment methods mentioned (Majumdar, 2011).

In consequence, the art continues to seek improvements in technology for analysis of routine spinal images and improvement of the quality and validity of measurements of disc degeneration and pathology obtained from those images. Ideally, a disc degeneration measure would produce precise, accurate measurements with high reliability, reproducibility, and solid evidence supporting validity. In addition, the measurement would be available through standard clinical imaging and would reflect desiccation and loss of structural integrity of the disc. Furthermore, the measurements would be simple and quick to obtain, preferably through automated image analysis software.

SUMMARY

The present disclosure relates to systems, non-transitory computer-readable media, and methods for assessing physiological condition of spinal intervertebral discs in a quantitative manner using magnetic resonance imaging (MRI) data. Such systems, non-transitory computer-readable media, and methods enable a measure of spinal disc health to be generated, wherein the measure is calculated using one or more ratios from signal-based measurements of spinal disc structures or regions, which can be obtained either through manual tracing or automated through programming of image analysis software. The use of ratios of selected disc regions applies knowledge of disc pathogenesis: on T2 weighted MR images, when the inner region (nucleus) of the disc degenerates it loses signal, whereas the dark outer zone (outer annulus) of the disc eventually increases in signal with degeneration.

In one aspect, the disclosure relates to computer-implemented methods of automatically quantifying spinal disc degeneration, the computer-implemented method comprising: receiving at a computer system an imaging data set including digitized imaging data of at least one spinal area; the computer system automatically calculating a first mean signal intensity for a first region of the at least one spinal area included in the imaging data set; the computer system automatically calculating a second mean signal intensity for a second region of the at least one spinal area in the imaging data set; and the computer system calculating a first value comprising calculation of a ratio of the first mean signal intensity to the second mean signal intensity, and wherein the ratio is substantially independent of signal intensity heterogeneity of the imaging data set, wherein the first value is indicative of a degree of spinal disc degeneration for one or more spinal discs in the at least one spinal area.

In another aspect, the disclosure relates to measurement and inclusion of an intermediate region in the calculation.

In a further aspect, the disclosure relates to measurement and inclusion of signal intensity specifically from anterior and posterior regions of the spine. As an example, using an axial image of the disc, the computer system automatically divides the disc into two to four, or more, regions and calculates the regions' mean signal intensities (FIGS. 5A-B). In the simplest case of two regions, the mean signal strength of the first outermost peripheral region (anatomically “outer annulus”) is the denominator and the mean signal strength of the second region (nucleus and inner annulus) is the numerator.

In a further aspect, the disclosure relates to measurement and inclusion of a specified portion of signal intensity pixels at the low end of the range within a region representing the entire disc on an axial or sagittal image, to represent the outer annulus. This technique can be applied by selecting the determined percent of pixels with the lowest intensity of the remaining pixels as the numerator. Such approach allows a simple ratio-based estimate of disc degeneration using based on internal disc structures.

A further aspect of the disclosure relates to a non-transitory computer-readable storage medium storing instructions executable by a computer system to automatically quantify spinal disc degeneration, the non-transitory computer-readable storage medium storing instructions to: receive at a computer system an imaging data set of digitized imaging data of at least one spinal area; calculate a first mean signal intensity for a first region of the at least one spinal area included in an imaging data set; calculate a second mean signal intensity for a second region of the at least one spinal area in the imaging data set; and calculate a first value comprising calculation of a ratio of the first mean signal intensity to the second mean signal intensity, wherein the first value is indicative of a degree of spinal disc degeneration for one or more spinal discs in the at least one spinal area, and wherein the ratio is substantially independent of signal intensity heterogeneity of the imaging data set.

A still further aspect of the disclosure relates to methods of assessing spinal disc health and obtaining a disc degeneration value, such methodology comprising the steps of: obtaining an MRI in digital form, determining the mean signal intensity of one or more nuclear regions, determining the mean signal intensity of one or more annular regions, and calculating a value representing disc health or a disc degeneration value, comprising calculation of one or more ratios of internal disc regions (e.g. a nuclear region to an annular region), using a computer-implemented analysis program comprising appertaining algorithm(s) for such calculation.

In another aspect, the disclosure relates to a therapeutic assessment and treatment method, comprising: obtaining selected MRI images of at least one spinal disc of a patient; digitizing the selected MRI images; selecting areas of the digitized images for input of corresponding area selections to a computer or other processor, for computational determination by the computer or other processor of a value indicative of spinal health of each of the at least one spinal disc of the patient based on at least one ratio of mean signal strength of a selected nuclear region to mean signal strength of a selected annular region of the at least one spinal disc of the patient; outputting by the computer or other processor of the value indicative of spinal health of each of the at least one spinal disc of the patient; and at least one of prescribing and conducting of therapeutic intervention comprising treatment of the patient, based on the outputted value indicative of spinal health of each of the at least one spinal disc of the patient.

In such method, the selecting of areas of the digitized image for input of corresponding area selections to a computer or other processor, may comprise manual tracing of areas of the digitized image. In other embodiments, the area selections are predetermined and computer-selected from the digitized images for input to the computer or other processor from an imaging apparatus. In still other embodiments, the therapeutic intervention comprises at least one of physical therapy and spinal disc surgery.

The disclosure in another aspect relates to an MRI imaging and computational system for determining spinal health of the patient, said system comprising: an MRI imaging apparatus configured to generate MRI images of at least one spinal disc of a patient and to digitize the MRI images; and a computer or other processor programmably configured to select areas of the digitized images for input of corresponding area selections to the computer or other processor, for computational determination by the computer or other processor of a value indicative of spinal health of each of the at least one spinal disc of the patient based on at least one ratio of mean signal strength of a selected nuclear region to mean signal strength of a selected annular region of the at least one spinal disc of the patient, and to output the value indicative of spinal health of each of the at least one spinal disc of the patient.

The MRI imaging and computational system may further comprise a database arranged to receive imaging data from the MRI imaging apparatus and computational data from the computer or other processor, for storage in the database, with the computer or other processor being configured to access the database and responsively generate from (i) newly generated patient data comprising at least one value indicative of spinal health of each of the at least one spinal disc of the patient, and (ii) archival data in the database, an output indicative of spinal disc health of the patient.

In such MRI imaging and computational system, the archival data in the database may comprise at least one of (a) historical spinal health disc data generated for the patient at a prior time or times, whereby the output comprises a longitudinal report of time-varying spinal disc health of the patient; (b) spinal health disc data for a patient population, whereby the output comprises a comparative report of spinal disc health of the patient in relation to the patient population, or a selected cohort sub-population thereof; (c) historical spinal health disc data generated for the patient at a prior time or times, wherein the computer or other processor is configured to generate a prognostic report for the patient comprising prognostic spinal disc health of the patient at a future time or times, based on the progression or character of prior spinal health disc data; and (d) spinal health disc data for a patient population, wherein the computer or other processor is configured to generate a prognostic report for the patient comprising prognostic spinal disc health of the patient at a future time or times, based on the progression or character of spinal health of the patient population, or a selected cohort subpopulation thereof. In other embodiments, the archival data in the database comprises at least two of archival data types (a)-(d).

The system as variously described above may comprise an MRI imaging apparatus configured to conduct T2 mapping of at least one spinal disc of the patient.

Other aspects, features, and advantages of the disclosure will be more fully apparent from the ensuing disclosure and claims.

