Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

Race and Gender Disparity in the Surgical Management of Hepatocellular Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Program Registry.

BACKGROUND: The existence of race and gender disparity has been described in numerous areas of medicine. The management of hepatocellular cancer is no different, but in no other area of medicine, is the treatment algorithm more complicated by local, regional, and national health care distribution policy. METHODS: Multivariate logistic regression and Cox-regression were utilized to analyze the treatment of patients with hepatocellular cancer registered in SEER between 1999 and 2013 to determine the incidence and effects of racial and gender disparity. Odd ratios (OR) are relative to Caucasian males, SEER region, and tumor characteristics. RESULTS: The analysis of 57,449 patients identified the minority were female (25.31%) and African-American (16.26%). All tumor interventions were protective (p < 0.001) with respect to survival. The mean survival for all registered patients was 13.01 months with conditional analysis, confirming that African-American men were less likely to undergo ablation, resection, or transplantation (p < 0.001). Women were more likely to undergo resection (p < 0.001). African-American women had an equivalent OR for resection but had a significantly lower transplant rate (p < 0.001). CONCLUSIONS: Utilizing SEER data as a surrogate for patient navigation in the treatment of hepatocellular cancer, our study identified not only race but gender bias with African-American women suffering the greatest. This is underscored by the lack of navigation of African-Americans to any therapy and a significant bias to navigate female patients to resection potentially limiting subsequent access to definitive therapy namely transplantation.

Diffusion model comparison identifies distinct tumor sub-regions and tracks treatment response.

PURPOSE: MRI biomarkers of tumor response to treatment are typically obtained from parameters derived from a model applied to pre-treatment and post-treatment data. However, as tumors are spatially and temporally heterogeneous, different models may be necessary in different tumor regions, and model suitability may change over time. This work evaluates how the suitability of two diffusion-weighted (DW) MRI models varies spatially within tumors at the voxel level and in response to radiotherapy, potentially allowing inference of qualitatively different tumor microenvironments. METHODS: DW-MRI data were acquired in CT26 subcutaneous allografts before and after radiotherapy. Restricted and time-independent diffusion models were compared, with regions well-described by the former hypothesized to reflect cellular tissue, and those well-described by the latter expected to reflect necrosis or oedema. Technical and biological validation of the percentage of tissue described by the restricted diffusion microstructural model (termed %MM) was performed through simulations and histological comparison. RESULTS: Spatial and radiotherapy-related variation in model suitability was observed. %MM decreased from a mean of 64% at baseline to 44% 6 days post-radiotherapy in the treated group. %MM correlated negatively with the percentage of necrosis from histology, but overestimated it due to noise. Within MM regions, microstructural parameters were sensitive to radiotherapy-induced changes. CONCLUSIONS: There is spatial and radiotherapy-related variation in different models' suitability for describing diffusion in tumor tissue, suggesting the presence of different and changing tumor sub-regions. The biological and technical validation of the proposed %MM cancer imaging biomarker suggests it correlates with, but overestimates, the percentage of necrosis.

Bile Leak Reduction with Laparoscopic Versus Open Liver Resection: A Multi-institutional Propensity Score-Adjusted Multivariable Regression Analysis.

INTRODUCTION: The reported rate of postoperative bile leak is variable between 3 and 33%. Recent data would suggest a minimally invasive approach to liver surgery has decreased this incidence. METHODS: This multi-institutional case-control study utilized databases from three high-volume surgeons. All consecutive open and minimally invasive liver resection cases were analyzed in a propensity score-adjusted multivariable regression. A p value < 0.05 was considered significant. RESULTS: In 1388 consecutive liver resections, the average age was 56.9 ± 14.0 years, 730 (52.59%) were male gender, and 599 (43.16%) underwent minimally invasive liver resection. Thirty-nine (2.81%) in the series were identified with post-resection bile duct leaks. Leaks were associated with major resections and increased blood loss (p < 0.05). Propensity score-adjusted multivariable regression identified minimally invasive liver resection significantly and independently reduced the odds of bile duct leak (OR 0.48, p = 0.046) even controlling for BMI, ASA, cirrhosis, major resection, and resection year. CONCLUSIONS: Our data suggest the incidence of bile leaks in a large-volume center series is far less than previously reported and that a minimally invasive approach to liver resection reduces the incidence of postoperative bile leak.

Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease.

BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.

Bile duct injury repairs: Progressive outcomes in a tertiary referral center.

BACKGROUND: Bile duct injury during laparoscopic cholecystectomy persists as a significant problem in general surgery, resulting in complex injuries, arterial damage, and post repair strictures. METHODS: We performed a retrospective analysis between 2 eras of bile duct injury repairs: 1987 to 2001 (n = 58) and 2002 to 2016 (n = 52) using logistic regression analyses to assess presentation, repair complexity, and outcomes. RESULTS: No differences in demographics, incidence of cholecystitis, conversion, time to presentation, level of injury, or arterial injury were identified. The second era had an increase in patient age, transhepatic catheter use, prior repair, and utilization of complex repairs. This approach resulted in equivalent complications and mortality rates with increased resource utilization but a lesser incidence of post-repair strictures (P = .004). Regression modeling correlated strictures to prior operative repairs (OR 4.25; P = .016) and a protective effect of repairs performed in the second era (OR 0.23; P = .045). CONCLUSION: The second era identified a decreasing trend of attempted repairs by referring surgeons but an increase in transhepatic catheters and complex repairs resulting in lesser rates of post-repair stricture. Final regression modeling confirmed increased operative experience decreased post-repair stricture reaffirming the benefits of early identification and referral of bile duct injuries to an experienced hepatobiliary surgeon at a specialty center.

Towards a 'resolution limit' for DW-MRI tumor microstructural models: A simulation study investigating the feasibility of distinguishing between microstructural changes.

PURPOSE: To determine the feasibility of extracting sufficiently precise estimates of cell radius, R, and intracellular volume fraction, fi , from DW-MRI data in order to distinguish between specific microstructural changes tissue may undergo, specifically focusing on cell death in tumors. METHODS: Simulations with optimized and non-optimized clinical acquisitions were performed for a range of microstructures, using a two-compartment model. The ability to distinguish between (i) cell shrinkage with cell density constant, mimicking apoptosis, and (ii) cell size constant with cell density decreasing, mimicking loss of cells, was evaluated based on the precision of simulated parameter estimates. Relationships between parameter precision, SNR, and the magnitude of specific parameter changes, were used to infer SNR requirements for detecting changes. RESULTS: Accuracy and precision depended on microstructural properties, SNR, and the acquisition protocol. The main benefit of optimized acquisitions tended to be improved accuracy and precision of R, particularly for small cells. In most cases considered, higher SNR was required for detecting changes in R than for changes in fi . CONCLUSIONS: Given the relative changes in R and fi due to apoptosis, simulations indicate that, for a range of microstructures, detecting changes in R require higher SNR than detecting changes in fi , and that such SNR is typically not achieved in clinical data. This suggests that if apoptotic cell size decreases are to be detected in clinical settings, improved SNR is required. Comparing measurement precision with the magnitude of expected biological changes should form part of the validation process for potential biomarkers.

Postrenal transplant infection: What is the effect of specific immunosuppressant agents?

BACKGROUND: Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections. METHODS: A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed. RESULTS: The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; P = .020) were protective. CONCLUSION: Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.

Racial and regional disparity in liver transplant allocation.

BACKGROUND: Sources of liver transplant disparities are not understood adequately, particularly in terms of race and region. METHODS: Fixed effects multivariate logistic regression augmented by modified forward and backward stepwise regression of transplanted patients from the United Network for Organ Sharing Standard Transplant Analysis and Research database (1985-2016) was performed to assess causal inference of such disparities. RESULTS: In the study sample (N = 258,602), significant disparities in the odds of receiving a liver were found: African Americans odds ratio 1.12 (95% confidence interval, 1.08-1.17), Asians 1.12 (95% confidence interval, 1.07-1.18), females 0.80 (95% confidence interval, 0.78-0.83), and malignancy 1.18 (95% confidence interval, 1.13-1.22). Region 7 (IL, MN, ND, SD, and WI) was set as the reference level since its transplantation rate most closely approximated the sex and race-matched rate of the national post-Share 35 average. Significant racial disparities by region were identified using Caucasian Region 7 as the reference: Hispanic Region 9 (New York, West Vermont) 1.22 (1.02-1.45), Hispanic Region 1 (New England) 1.26 (1.01-1.57), Hispanic Region 4 (Oklahoma, TX) 1.23 (1.05-1.43), and Asian Region 4 (Oklahoma, TX) 1.35 (1.05-1.73). CONCLUSION: Despite numerous adjustments to liver allocation, we identified with causal inference statistics on a large dataset spanning ≥30 years there remain racial and regional overweighting.

A biomimetic tumor tissue phantom for validating diffusion-weighted MRI measurements.

PURPOSE: To develop a biomimetic tumor tissue phantom which more closely reflects water diffusion in biological tissue than previously used phantoms, and to evaluate the stability of the phantom and its potential as a tool for validating diffusion-weighted (DW) MRI measurements. METHODS: Coaxial-electrospraying was used to generate micron-sized hollow polymer spheres, which mimic cells. The bulk structure was immersed in water, providing a DW-MRI phantom whose apparent diffusion coefficient (ADC) and microstructural properties were evaluated over a period of 10 months. Independent characterization of the phantom's microstructure was performed using scanning electron microscopy (SEM). The repeatability of the construction process was investigated by generating a second phantom, which underwent high resolution synchrotron-CT as well as SEM and MR scans. RESULTS: ADC values were stable (coefficients of variation (CoVs) < 5%), and varied with diffusion time, with average values of 1.44 ± 0.03 µm2 /ms (Δ = 12 ms) and 1.20 ± 0.05 µm2 /ms (Δ = 45 ms). Microstructural parameters showed greater variability (CoVs up to 13%), with evidence of bias in sphere size estimates. Similar trends were observed in the second phantom. CONCLUSION: A novel biomimetic phantom has been developed and shown to be stable over 10 months. It is envisaged that such phantoms will be used for further investigation of microstructural models relevant to characterizing tumor tissue, and may also find application in evaluating acquisition protocols and comparing DW-MRI-derived biomarkers obtained from different scanners at different sites. Magn Reson Med 80:147-158, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: How do permeability and perfusion vary between human tumours?

BACKGROUND: Solid tumours exhibit enhanced vessel permeability and fenestrated endothelium to varying degree, but it is unknown how this varies in patients between and within tumour types. Dynamic contrast-enhanced (DCE) MRI provides a measure of perfusion and permeability, the transfer constant Ktrans, which could be employed for such comparisons in patients. AIM: To test the hypothesis that different tumour types exhibit systematically different Ktrans. MATERIALS AND METHODS: DCE-MRI data were retrieved from 342 solid tumours in 230 patients. These data were from 18 previous studies, each of which had had a different analysis protocol. All data were reanalysed using a standardised workflow using an extended Tofts model. A model of the posterior density of median Ktrans was built assuming a log-normal distribution and fitting a simple Bayesian hierarchical model. RESULTS: 12 histological tumour types were included. In glioma, median Ktrans was 0.016min-1 and for non-glioma tumours, median Ktrans ranged from 0.10 (cervical) to 0.21min-1 (prostate metastatic to bone). The geometric mean (95% CI) across all the non-glioma tumours was 0.15 (0.05, 0.45)min-1. There was insufficient separation between the posterior densities to be able to predict the Ktrans value of a tumour given the tumour type, except that the median Ktrans for gliomas was below 0.05min-1 with 80% probability, and median Ktrans measurements for the remaining tumour types were between 0.05 and 0.4min-1 with 80% probability. CONCLUSION: With the exception of glioma, our hypothesis that different tumour types exhibit different Ktrans was not supported. Studies in which tumour permeability is believed to affect outcome should not simply seek tumour types thought to exhibit high permeability. Instead, Ktrans is an idiopathic parameter, and, where permeability is important, Ktrans should be measured in each tumour to personalise that treatment.

Initial Experience With Biologic Polymer Scaffold (Poly-4-hydroxybuturate) in Complex Abdominal Wall Reconstruction.

OBJECTIVE: To evaluate the use of the new absorbable polymer scaffold poly-4-hydroxybutyrate (P4HB) in complex abdominal wall reconstruction. BACKGROUND: Complex abdominal wall reconstruction has witnessed tremendous success in the last decade after the introduction of cadaveric biologic scaffolds. However, the use of cadaveric biologic mesh has been expensive and plagued by complications such as seroma, infection, and recurrent hernia. Despite widespread application of cadaveric biologic mesh, little data exist on the superiority of these materials in the setting of high-risk wounds in patients. P4HB, an absorbable polymer scaffold, may present a new alternative to these cadaveric biologic grafts. METHODS: A retrospective analysis of our initial experience with the absorbable polymer scaffold P4HB compared with a consecutive contiguous group treated with porcine cadaveric mesh for complex abdominal wall reconstructions. Our analysis was performed using SAS 9.3 and Stata 12. RESULTS: The P4HB group (n = 31) experienced shorter drain time (10.0 vs 14.3 d; P < 0.002), fewer complications (22.6% vs 40.5%; P < 0.046), and reherniation (6.5% vs 23.8%; P < 0.049) than the porcine cadaveric mesh group (n = 42). Multivariate analysis for infection identified: porcine cadaveric mesh odds ratio 2.82, length of stay odds ratio 1.11; complications: drinker odds ratio 6.52, porcine cadaveric mesh odds ratio 4.03, African American odds ratio 3.08, length of stay odds ratio 1.11; and hernia recurrence: porcine cadaveric mesh odds ratio 5.18, drinker odds ratio 3.62, African American odds ratio 0.24. Cost analysis identified that P4HB had a $7328.91 financial advantage in initial hospitalization and $2241.17 in the 90-day postdischarge global period resulting in $9570.07 per case advantage over porcine cadaveric mesh. CONCLUSIONS: In our early clinical experience with the absorbable polymer matrix scaffold P4HB, it seemed to provide superior clinical performance and value-based benefit compared with porcine cadaveric biologic mesh.

Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis.

BACKGROUND: Amniotic membrane is tissue obtained from human placenta rich in cytokines, growth factors, and stem cells that possess the ability to inhibit infection, improve healing, and stimulate regeneration. METHODS: A meta-analysis was performed examining randomized controlled trials comparing amniotic tissue products with standard of care in nonhealing diabetic foot ulcers including PubMed, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. RESULTS: A search of 3 databases identified 596 potentially relevant articles. Application of selection criteria led to the selection of 5 randomized controlled trials. The 5 selected randomized controlled trials represented a total of 311 patients. The pooled relative risk of healing with amniotic products compared with control was 2.7496 (2.05725-3.66524, P < 0.001). CONCLUSIONS: The current meta-analysis indicates that the treatment of diabetic foot ulcers with amniotic membrane improves healing rates in diabetic foot ulcers. Further studies are needed to determine whether these products also decrease the incidence of subsequent complications, such as amputation or death, in diabetic patients.

T1 Relaxation Time in Lungs of Asymptomatic Smokers.

PURPOSE: Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers. MATERIALS AND METHODS: Lung T1 measurements from 35 subjects, 23 never smokers and 12 current smokers were retrospectively analyzed from an institutional review board approved study. All 35 subjects underwent pulmonary function test (PFT) measurements and lung T1, with similar T1 measurement protocols. A backward linear model of T1 as a function of FEV1, FVC, weight, height, age and PY was tested. RESULTS: A significant correlation between lung T1 and PY was found with a negative slope of -3.2 ms/year (95% confidence interval [CI] [-5.8, -0.6], p = 0.02), when adjusted for age and height. Lung T1 shortens with ageing among all subjects, -4.0 ms/year (95%CI [-6.3, -1.7], p = 0.001), and among the never smokers, -3.7 ms/year (95%CI [-6.0, -1.3], p = 0.003). CONCLUSIONS: A correlation between lung T1 and PY when adjusted for both age and height was found, and T1 of the lung shortens with ageing. Accordingly, PY and age can be significant confounding factors when T1 is used as a biomarker in lung MRI studies that must be taken into account to detect underlying patterns of disease.

COPD Patients Have Short Lung Magnetic Resonance T1 Relaxation Time.

Magnetic resonance imaging (MRI) may provide attractive biomarkers for assessment of pulmonary disease in clinical trials as it is free from ionizing radiation, minimally invasive and allows regional information. The aim of this study was to characterize lung MRI T1 relaxation time as a biomarker of chronic obstructive pulmonary disease (COPD); and specifically its relationship to smoking history, computed tomography (CT), and pulmonary function test (PFT) measurements in comparison to healthy age-matched controls. Lung T1 and inter-quartile range (IQR) of T1 maps from 24 COPD subjects and 12 healthy age-matched non-smokers were retrospectively analyzed from an institutional review board approved study. The subjects underwent PFTs and two separate MR imaging sessions at 1.5 tesla to test T1 repeatability. CT scans were performed on the COPD subjects. T1 repeatability (intraclass correlation coefficient) was 0.72 for repeated scans acquired on two visits. The lung T1 was significantly shorter (p < 0.0001) and T1 IQR was significantly larger (p = 0.0002) for the COPD subjects compared to healthy controls. Lung T1 significantly (p = 0.001) correlated with lung density assessed with CT. Strong significant correlations (p < 0.0001) between lung T1 and all PFT measurements were observed. Cigarette exposure did not correlate with lung T1 in COPD subjects. In conclusion, lung MRI T1 mapping shows potential as a repeatable, radiation free, non-invasive imaging technique in the evaluation of COPD.

Respiratory tract exacerbations revisited: ventilation, inflammation, perfusion, and structure (VIPS) monitoring to redefine treatment.

For cystic fibrosis (CF) patients older than 6 years there are convincing data that suggest respiratory tract exacerbations (RTE) play an important role in the progressive loss of functional lung tissue. There is a poor understanding of the pathobiology of RTE and whether specific treatment of RTE reduces lung damage in the long term. In addition, there are limited tools available to measure the various components of CF lung disease and responses to therapy. Therefore, in order to better understand the impact of RTE on CF lung disease we need to develop sensitive measures to characterize RTE and responses to treatment; and improve our understanding of structure-function changes during treatment of RTE. In this paper we review our current knowledge of the impact of RTE on the progression of lung disease and identify strategies to improve our understanding of the pathobiology of RTE. By improving our knowledge regarding RTE in CF we will be better positioned to develop approaches to treatment that are individualized and that can prevent permanent structural damage. We suggest the development of a ventilation, perfusion, inflammation and structure (VIPS)-MRI suite that supplies the clinician with data on ventilation, inflammation, perfusion, and structure in one MRI session. VIPS-MRI could be an important step to better understand the factors that contribute to and limit treatment efficacy of RTE.

Ground Truth for Diffusion MRI in Cancer: A Model-Based Investigation of a Novel Tissue-Mimetic Material.

This work presents preliminary results on the development, characterisation, and use of a novel physical phantom designed as a simple mimic of tumour cellular structure, for diffusion-weighted magnetic resonance imaging (DW-MRI) applications. The phantom consists of a collection of roughly spherical, micron-sized core-shell polymer 'cells', providing a system whose ground truth microstructural properties can be determined and compared with those obtained from modelling the DW-MRI signal. A two-compartment analytic model combining restricted diffusion inside a sphere with hindered extracellular diffusion was initially investigated through Monte Carlo diffusion simulations, allowing a comparison between analytic and simulated signals. The model was then fitted to DW-MRI data acquired from the phantom over a range of gradient strengths and diffusion times, yielding estimates of 'cell' size, intracellular volume fraction and the free diffusion coefficient. An initial assessment of the accuracy and precision of these estimates is provided, using independent scanning electron microscope measurements and bootstrap-style simulations. Such phantoms may be useful for testing microstructural models relevant to the characterisation of tumour tissue.

Mixed-effects modeling of clinical DCE-MRI data: application to colorectal liver metastases treated with bevacizumab.

PURPOSE: Most dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data are evaluated for individual patients with cohorts analyzed to detect significant changes from baseline values, repeating the process at each posttreatment timepoint. Our study aimed to develop a statistically valid model for the complete time course of DCE-MRI data in a patient cohort. MATERIALS AND METHODS: Data from 10 patients with colorectal cancer liver metastases were analyzed, including two baseline scans and four post-bevacizumab scans. Apparent changes in tumor median K(trans) were adjusted for changes in observed enhancing tumor fraction (EnF) by multiplying K(trans) by EnF (KEnF). A mixed-effects model (MEM) was defined to describe the KEnF time course for all patients simultaneously by assuming a three-parameter indirect response model with model parameters lognormally distributed across patients. RESULTS: The typical cohort time course showed a KEnF reduction to 59% of baseline at 24 hours, returning to 65% of baseline values by day 12. Interpatient variability of model parameters ranged from 11% to 307%. CONCLUSION: The MEM approach has potential for comparing responses at a group level in clinical trials with different doses, schedules, or combination regimens. Furthermore, the KEnF biomarker successfully resolved confounds in interpreting K(trans) arising from therapy induced changes in the volume of enhancing tumor.