The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> The effects of critical illness on extracellular water (ECW) and total body water (TBW) were measured using (1) a multiple dilutional technique, and (2) whole body and regional bioelectrical impedance analysis (BIA) in a group of stable patients. Total body water and body resistance (R) were similar in patients when compared with normal healthy subjects (TBW: 45.1±4.5 vs. 46.2±3.4 L, p=0.85; R: 518±42 vs. 500±22Ω, p=0.70), and a significant relationship was present between these measurements (r=-0.87, p<0.001) <s> BIB001 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution. <s> BIB002 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> Electrical impedance spectrometry is an important application field of bioimpedance measurements. After introducing the electrical properties of biological tissues, this part presents instrumental aspects and applications of electrical impedance spectrometry. The main instrumental constraints encountered in spectrometric electrical impedance measurements are reviewed, focusing on low-frequency applications. Examples of impedance cells and probes are presented and several instrumental setups operating in the frequency and time domain are described. Some examples of applications are presented, including in vitro characterization and modeling of normal tissues, in vitro and in vivo characterization of cancerous tissues, and assessment of tissue perfusion/ischemia levels. <s> BIB003 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> Measurements of extracellular water (ECW) and total body water (TBW) can be useful when assessing the nutritional status of surgical patients. The simple and non-invasive nature of bio-impedance techniques may allow repeat measurements to assess clinically significant changes in ECW and TBW. We have evaluated bio-impedance spectroscopy (BIS) and multi-frequency bio-impedance analysis (MFBIA) using radioisotope dilution as the independent method. <s> BIB004 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> : The effects of an episode of acute classical dengue fever on extracellular water (ECW), intracellular water (ICW), and total body water (TBW) were measured in nine patients using conventional dilution techniques; and the findings were compared with the outcome variables from whole body impedance spectroscopy (BIS), extracellular fluid resistance (Recf), and intracellular fluid resistance (Ricf). The patients were assessed on admission with febrile presentation (DI), at discharge after the defervescence of the fever cycle at about five days postadmission (DII), and seven days thereafter (DIII). As a reference group, 15 persons without acute or chronic illness were enrolled. Total body water was unaltered during the course of disease and was not different from that in normal healthy subjects. However, body water shifted from the intracellular to the extracellular compartment in patients from the acute phase to convalescence, as reflected in the ratios of ECW/TBW and ECW/ICW. These ratios were significantly higher in convalescent dengue patients (DIII) than in the reference group (p < 0.05). Increasing ECW, from the acute phase of the disease to convalescence, was associated with a significant decrease in Recf (719 ± 95, 693 ± 89, 643 ± 81 Ω; p < 0.0001) and in Recf/Ricf (p < 0.01). Recf and Recf/Ricf were higher in the acute phase (DI) of dengue fever compared to controls (p < 0.05). We conclude that dengue fever is characterized by a relative expansion of ECW during the course of disease and convalescence. BIS was sensitive in determining the hydrational profile in dengue fever patients. <s> BIB005 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> Abstract Dengue haemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage and a period of increased microvascular permeability. Monitoring of plasma volume and body fluid compartment shifts is an integral part of the clinical management of DHF, and is crucial to the performance of clinical research studies on DHF pathogenesis. Multifrequency bioelectrical impedance spectroscopy (BIS) was assessed as a non-invasive method to monitor body fluid compartment shifts in children participating in a prospective, hospital-based, study of dengue virus infections in Thailand. Over the 48 h surrounding defervescence, the extracellular water/intracellular water ratio (ECW/ICW) rose in children with dengue virus infections and correlated with increasing disease severity [DHF > intermediate dengue fever (DF)/DHF>DF]. Plasma leakage remained within the ECW compartment and was not directly measured by multifrequency BIS. Expansion of the ECW space in DHF appeared to be primarily due to diminished renal water clearance. During the course of dengue illness, multifrequency BIS did not improve on serial haematocrit and bodyweight determinations for monitoring plasma volume contraction and ECW expansion, respectively. <s> BIB006 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> This paper describes a model for predicting hemoglobin (Hb) by using bioelectrical impedance analysis (BIA) in dengue patients in the Hospital Universiti Kebangsaan Malaysia (HUKM). Bioelectrical impedance measurements were conducted on 83 (47 males and 36 females) serologically confirmed dengue fever (DF) and dengue hemorrhagic fever (DHF) patients during their hospitalization. The predictive equation for Hb was derived using multivariate analysis. We investigated all the parameters in BIA, patients' symptom and demographic data. In this developed model, four predictors (reactance (Xc), sex, weight and vomiting) were found to be the best predictive factors for modeling Hb in dengue patients. However, the model can only explain approximately 42% of the variation in Hb status, thus single frequency bio-impedance stand-alone technique is insufficient to monitor Hb for the DF and DHF patients. Further investigation using multi-frequency BIA is recommended in modeling Hb to achieve the most parsimonious model. <s> BIB007 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> This paper introduces a novel approach to classify the risk in dengue hemorrhagic fever (DHF) patients using the bioelectrical impedance analysis (BIA) technique. This in vivo technique involves the application of a small average constant current of less than 1 mA at a single frequency of 50 kHz through the human body, and measurement of the body's bioelectrical resistance (R), phase angle (/spl alpha/), body capacitance (BC) and capacitive reactance (X/sub c/) via four surface electrodes. BIA measurements have been conducted on 184 (97 males and 87 females) serological confirmed dengue patients during their hospitalization in University Kebangsaan Malaysia Hospital, Malaysia. The patients included in the study were DHF I-IV according to World Health Organization criteria. Univariate analysis of variance is used for assessing the relationship between gender and group with the bioelectrical tissue conductivity (BETC) parameters. Experimental findings show that BETC, as reflected by reactance, is the key determinant indicator for classifying risk category in the DHF patients. Hence, this novel approach of the BIA technique can provide a rapid, noninvasive, and promising method for classifying and evaluating the risk of the DHF patients. <s> BIB008 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> This paper describes the water compartments in healthy subjects and dengue patients on the day of defervescence of fever using bioelectrical impedance analysis. A total of 223 healthy subjects (65 males and 158 females) and 210 dengue patients (119 males and 91 females) in Hospital Universiti Kebangsaan Malaysia (HUKM), were studied. The ages for healthy subjects vary between 14 and 60 years old with mean age of 26.05 years while the ages for the dengue patients vary between 12 and 83 years old with mean age of 30.14 years. The parameters of water compartments investigated were total body water (TBW), extracellular water (ECW) and intracellular water (ICW). There were significant difference between healthy subjects and dengue patients for both male (p<0.05) and female (p<0.001) beginning on fever day 0 till fever day 4. The mean TBW and ECW values of dengue patients obtained were found to be higher than the normal healthy subjects while the mean ICW was lower. The mean TBW and ICW for male were higher than female while the mean ECW for male was lower than female for healthy subjects and dengue patients. <s> BIB009 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> This study presents a new approach to determine the significant prognosis factors in dengue patients utilizing the self-organizing map (SOM). SOM was used to visualize and determine the significant factors that can differentiate between the dengue patients and the healthy subjects. Bioimpedance analysis (BIA) parameters and symptoms/signs obtained from the 210 dengue patients during their hospitalization were used in this study. Database comprised of 329 sample (210 dengue patients and 119 healthy subjects) were used in the study. Accordingly, two maps were constructed. A total of 35 predictors (17 BIA parameters, 18 symptoms/signs) were investigated on the day of defervescence of fever. The first map was constructed based on BIA parameters while the second map utilized the symptoms and signs. The visualized results indicated that, the significant BIA prognosis factors for differentiating the dengue patients from the healthy subjects are reactance, intracellular water, ratio of the extracellular water and intracellular water, and ratio of the extracellular mass and body cell mass. <s> BIB010 </s> The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review <s> Bioelectrical Impedance <s> The interdigitated electrodes and electrical measurements for the diagnosis of dengue infection using antigen-antibody conjugation method are reported. As a proof of concept, pre-inactivated dengue virus was firstly immobilized indirectly onto the immunosensor surface, pre-coated with solgel derived BST thin film and organic self-assembled monolayer (SAM) over the interdigitated electrodes. The modified sensor surface served as selective sensing probe to capture/conjugate the anti-dengue antibody molecules present in patient's serum. Our immunosensor is based on non-faradaic process, using only DI water as electrolyte during the simple electrical measurements. Both ac impedance spectroscopy and dc I-V measurements between the electrodes gave a clearly discernable and repeatable signal to positively identify the presence of dengue antibody in the serum. Direct correlation was obtained between the signal outputs with respect to antibody concentrations. The measured signal changes in impedance/current without/with the presence of dengue antibody were attributed to the surface conductivity change upon biomolecules immobilization and the dipole-induced interfacial polarization potential at the SAM film/biomolecules interface. By monitoring the impedance or current change, the antibody molecules in the patient's serum could be positively detected. <s> BIB011
Over the years, bioelectrical impedance analysis (BIA) has demonstrated its utility as a non-invasive method for measurement and diagnosis in several medical applications. BIA evaluates the human body composition such as mass distribution (i.e., body cell mass and extracellular mass), and water compartments (i.e., intracellular water, extracellular water) by passing a small current through it BIB003 . The majority of the impedance measurements use four electrodes to minimize electrode-skin impedance effects. A small high-frequency current (50 kHz) is passed between two of the electrodes while the voltage drop across the same area is then measured using the other pair of electrodes. The ratio of the voltage drop to the current determines the resistance and reactance (Xc) of the body segment being measured. This data can then estimate the extracellular water (ECW), intracellular water (ICW), fat free mass (FFM), and fat mass through recognized equations  . BIA and bioelectrical impedance spectroscopy (BIS) have been described as a potentially reliable method to assess clinically significant changes in extracellular and total body water in dengue patients BIB001   BIB004 BIB002 . It could be a useful tool as a proxy for formal dilution methods to assess fluid shifts. Pierson and Wang (1986) have also proposed that an elevation of the extracellular water (ECW)/intracellular water (ICW) ratio in dengue patients, determined by dilution techniques, is a sensitive but nonspecific marker for the presence of systemic disease, and total body impedance measurements are especially useful in this determination. In dengue infections several approaches were followed for utilizing the BIA technique. The hydrational profile which reflects the distribution of body water between the intra and extracellular space in dengue patients was investigated  BIB008 BIB009  BIB005 BIB006  . Studies conducted by Klassen et al. BIB005 , Ibrahim et al.  , and Mazariegos et al.  have shown that BIA was sensitive in determining the hydrational profile in dengue patients. Klassen et al. BIB005 studied the changes in hydrational status during the acute phase of classical dengue fever in 9 adult patients. They studied the effects of the acute classical dengue fever on ECW, ICW, and total body water (TBW) by comparing conventional dilution techniques with the outcome variables from whole body impedance spectroscopy (BIS), extracellular fluid resistance (Recf), and intracellular fluid resistance (Ricf) BIB005 . Two groups were investigated: a reference group comprised of 15 subjects without acute or chronic illness and dengue patients. The dengue patients were investigated on admission with febrile presentation (DI), at discharge after the defervescence of the fever cycle at about five days post-admission (DII), and seven days thereafter (DIII). The results revealed that the total body water did not change during the course of the disease and was not different from that in normal healthy subjects. However, the ratios of ECW/TBW and ECW/ICW reflected that body water shifted from the intracellular to the extracellular compartment in patients from the acute phase to convalescence. This ratio was also higher in convalescent dengue patients (DIII) compared to the reference group. The results also showed an association between increasing ECW, from the acute phase of the disease to convalescence and decreasing the Recf and the Recf/Ricf ratio. Moreover, the Recf and Recf/Ricf values were higher in the acute phase (DI) of dengue fever compared to those of the non-dengue subjects. The study concluded that relative expansion of ECW during the course of the disease and in the convalescence stage as determined by measuring body impedance can be used to monitor the dengue fever progression. Fang et al. BIB011 reported a biosensor platform for dengue fever detection from patient serum. Their sensor was based on a non-faradic process where an integrated sensor captures the dengue antibody selectively from the sample. A thin film of sol-gel derived barium strontium titanate (BST) was coated on the immunosensor surface, and then the surface was modified with an organic self-assembled monolayer (SAM). In addition, pre-inactivated dengue virus was indirectly immobilized on the surface to act as a sensing probe to capture the dengue antibody. Finally, the modified surface was based on a finger shaped electrode where the output impedance/current will change in correlation with the presence and concentrations of dengue antibody in the serum sample. The work was conducted at frequency ranges of 0.1 Hz to 1 MHz. Ibrahim et al. BIB007 monitored and modelled the hemoglobin (Hb) status in dengue patients using the BIA parameters. The Hb status was used since it is directly related to the Hct status which can be used to determine the degree of microvascular permeability in dengue patients. The BIA was employed to construct a model for predicting Hb in dengue patients using the multivariate analysis technique. Eighty-three (47 males and 36 females) serologically confirmed DF and DHF patients were studied during their hospitalization. The data consisted of all the investigated parameters in BIA, patientsʼ symptoms, and demographic data. Four predictors: reactance, gender, weight, and vomiting were found to be the most significant parameters for predicting the Hb levels in dengue patients. The study concluded that the single frequency bio-impedance technique and Multiple-linear-regression analysis is insufficient to monitor Hb for dengue patients since this analysis only explains approximately 42% of the Hb variation. This model has been enhanced by utilizing a non-linear artificial neural network (ANN) and achieved 74% accuracy BIB010 . The graphical user interface for the model is shown in Figure 1 . The enhanced model is able to predict the Hb concentration which helps to determine the degree of microvascular permeability in dengue patients based on the above mentioned data. Additional enhancement of the model was achieved by employing the nonlinear autoregressive moving average with exogenous input (NARMAX) approach  . Three different NARMAX model order selection criteria, namely FPE, AIC, and Lipschitz were evaluated. The results gave 88.40% prediction accuracy by using the Lipschitz number approach. The study concluded that the NARMAX model yields better accuracy compared to the autoregressive moving average with exogenous input (ARMAX) model which achieved 76.70% accuracy. 