Survey of peer review programs among pediatric radiologists: report from the SPR Quality and Safety Committee.

During the last 15 years, peer review has been widely incorporated into radiology quality improvement programs. However, current implementations are variable and carry concerns, including subjectivity of numerical scores and a sense of merely satisfying regulatory requirements. The Society for Pediatric Radiology (SPR) Quality and Safety Committee sought to evaluate the state of peer review programs in pediatric radiology practices, including implementation methods, perceived functions, strengths and weaknesses, and opportunities for improvement. We distributed an online 16-question survey to SPR members. Questions pertained to the type of peer review system, the use of numerical scores and comments, how feedback on discordances is given and received, and the use of peer learning conferences. We collected 219 responses (15% of survey invitations), 80% of which were from children's hospitals. Fifty percent of respondents said they use a picture archiving and communication system (PACS)-integrated peer review system. Comment-enhanced feedback for interpretive discordances was either very important or somewhat important to performance improvement in 86% of responses, compared to 48% with a similar perception of numerical scores. Sixty-eight percent of respondents said they either rarely or never check their numerical scores, and 82% either strongly or somewhat agreed that comments are more effective feedback than numerical scores. Ninety-three percent either strongly or somewhat agreed that peer learning conferences would be beneficial to their practice. Forty-eight percent thought that their current peer review system should be modified. Survey results demonstrate that peer review systems in pediatric radiology practices are implemented variably, and nearly half of respondents believe their systems should be modified. Most respondents prefer feedback in the form of comments and peer learning conferences, which are thought to be more beneficial for performance improvement than numerical scores.

Radiation dose management for pediatric cardiac computed tomography: a report from the Image Gently 'Have-A-Heart' campaign.

Children with congenital or acquired heart disease can be exposed to relatively high lifetime cumulative doses of ionizing radiation from necessary medical imaging procedures including radiography, fluoroscopic procedures including diagnostic and interventional cardiac catheterizations, electrophysiology examinations, cardiac computed tomography (CT) studies, and nuclear cardiology examinations. Despite the clinical necessity of these imaging studies, the related ionizing radiation exposure could pose an increased lifetime attributable cancer risk. The Image Gently "Have-A-Heart" campaign is promoting the appropriate use of medical imaging studies in children with congenital or acquired heart disease while minimizing radiation exposure. The focus of this manuscript is to provide a comprehensive review of radiation dose management and CT performance in children with congenital or acquired heart disease.

Reducing Fluoroscopic Radiation Exposure During Endomyocardial Biopsy in Pediatric Transplant Recipients.

Endomyocardial biopsy (EMB) with fluoroscopy is used for rejection surveillance in pediatric heart transplantation. Lowering frame rate may reduce radiation, but decreases temporal resolution and image quality. We undertook a quality initiative reducing frame rate from 10 frames per second (FPS) to 5 FPS. To assess whether lowering frame rate can reduce radiation exposure without compromising safety, data on EMBs from 9/2009 to 4/2013 without angiography or intervention were reviewed. Effective dose was calculated from dose area product (DAP) and fluoroscopy time. Complications were reviewed. Independent t test compared pre- and post-data and a general linear model were used to control for confounders. Paired t test of most proximate data was used for pts with EMB before and after our change. Eighty-six patients had 543 EMB. After adjusting for weight, attending, and presence of a fellow, the lower FPS group had a 60.3% reduction in DAP (p < 0.0001) and 53.8% drop in effective dose (p < 0.0001). Fluoroscopy time did not differ. Twenty-eight pts had EMBs both before and after the FPS change. Pair-wise analysis of this group demonstrated a 33% reduction in DAP (p < 0.05) and 37% drop in effective dose (p < 0.01), without difference in fluoroscopy time. No patient had an increase in TR > 1 grade by ECHO. There were no deaths or perforations. Lowering the frame rate reduces radiation exposure by >50% without compromising safety. Efforts to further minimize radiation exposure of this vulnerable population should be considered.

Implementation of a comprehensive MR safety course for medical students.

This review article proposes the design of an educational magnetic resonance (MR) safety course for instructing medical students about basic MR and patient-related safety. The MR safety course material can be implemented as a traditional didactic or interactive lecture in combination with hands-on safety demonstrations. The goal of the course is to ensure that medical students receive a basic understanding of MR principles and safety considerations. This course will prepare medical students for patient screening and safety consultations when ordering MR studies. A multiple-choice exam can be used to document the proficiency in MR safety of the medical students. The course can be used by various medical school programs and may help to ensure consistent quality of teaching materials and MR safety standards.

MR characterization of hepatic storage iron in transfusional iron overload.

PURPOSE: To quantify the two principal forms of hepatic storage iron, diffuse, soluble iron (primarily ferritin), and aggregated, insoluble iron (primarily hemosiderin) using a new MRI method in patients with transfusional iron overload. MATERIALS AND METHODS: Six healthy volunteers and 20 patients with transfusion-dependent thalassemia syndromes and iron overload were examined. Ferritin- and hemosiderin-like iron were determined based on the measurement of two distinct relaxation parameters: the "reduced" transverse relaxation rate, RR2 , and the "aggregation index," A, using three sets of Carr-Purcell-Meiboom-Gill (CPMG) datasets with different interecho spacings. Agarose phantoms, simulating the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron, were used for validation. RESULTS: Both phantom and in vivo human data confirmed that transverse relaxation components associated with the dispersed and aggregated iron could be separated using the two-parameter (RR2 , A) method. The MRI-determined total hepatic storage iron was highly correlated (r = 0.95) with measurements derived from biopsy or biosusceptometry. As total hepatic storage iron increased, the proportion stored as aggregated iron became greater. CONCLUSION: This method provides a new means for noninvasive MRI determination of the partition of hepatic storage iron between ferritin and hemosiderin in iron overload disorders.

Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status.

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

A Scalable Database of Organ Doses for Common Diagnostic Fluoroscopy Procedures of Children: Procedures of Historical Practice for Use in Radiation Epidemiology Studies.

Assessment of health effects from low-dose radiation exposures in patients undergoing diagnostic imaging is an active area of research. High-quality dosimetry information pertaining to these medical exposures is generally not readily available to clinicians or epidemiologists studying radiation-related health risks. The purpose of this study was to provide methods for organ dose estimation in pediatric patients undergoing four common diagnostic fluoroscopy procedures: the upper gastrointestinal (UGI) series, the lower gastrointestinal (LGI) series, the voiding cystourethrogram (VCUG) and the modified barium swallow (MBS). Abstracted X-ray film data and physician interviews were combined to generate procedure outlines detailing X-ray beam projections, imaged anatomy, length of X-ray exposure, and presence and amount of contrast within imaged anatomy. Monte Carlo radiation transport simulations were completed for each of the four diagnostic fluoroscopy procedures across the 162-member (87 males and 75 females) University of Florida/National Cancer Institute pediatric phantom library, which covers variations in both subject height and weight. Absorbed doses to 28 organs, including the active marrow and bone endosteum, were assigned for all 162 phantoms by procedure. Additionally, we provide dose coefficients (DCs) in a series of supplementary tables. The DCs give organ doses normalized to procedure-specific dose metrics, including: air kerma-area product (µGy/mGy · cm2), air kerma at the reference point (µGy/µGy), number of spot films (SF) (µGy/number of SFs) and total fluoroscopy time (µGy/s). Organs accumulating the highest absorbed doses per procedure were as follows: kidneys between 0.9-25.4 mGy, 1.1-16.6 mGy and 1.1-9.7 mGy for the UGI, LGI and VCUG procedures, respectively, and salivary glands between 0.2-3.7 mGy for the MBS procedure. Average values of detriment-weighted dose, a phantom-specific surrogate for the effective dose based on ICRP Publication 103 tissue-weighting factors, were 0.98 mSv, 1.16 mSv, 0.83 mSv and 0.15 mSv for the UGI, LGI, VCUG and MBS procedures, respectively. Scalable database of organ dose coefficients by patient sex, height and weight, and by procedure exposure time, reference point air kerma, kerma-area product or number of spot films, allows clinicians and researchers to compute organ absorbed doses based on their institution-specific and patient-specific dose metrics. In addition to informing on patient dosimetry, this work has the potential to facilitate exposure assessments in epidemiological studies designed to investigate radiation-related risks.

Subjective and objective evaluation of image quality in biplane cerebral digital subtraction angiography following significant acquisition dose reduction in a clinical setting.

OBJECTIVE: Different technical and procedural methods have been introduced to develop low radiation dose protocols in neurointerventional examinations. We investigated the feasibility of minimizing radiation exposure dose by simply decreasing the detector dose during cerebral DSA and evaluated the comparative level of image quality using both subjective and objective methods. METHODS: In a prospective study of patients undergoing diagnostic cerebral DSA, randomly selected vertebral arteries (VA) and/or internal carotid arteries and their contralateral equivalent arteries were injected. Detector dose of 3.6 and 1.2 µGy/frame were selected to acquire standard dose (SD) and low dose (LD) images, respectively. Subjective image quality assessment was performed by two neurointerventionalists using a 5 point scale. For objective image quality evaluation, circle of Willis vessels were categorized into conducting, primary, secondary, and side branch vessels. Two blinded observers performed arterial diameter measurements in each category. Only image series obtained from VA injections opacifying the identical posterior intracranial circulation were utilized for objective assessment. RESULTS: No significant difference between SD and LD images was observed in subjective and objective image quality assessment in 22 image series obtained from 10 patients. Mean reference air kerma and kerma area product were significantly reduced by 61.28% and 61.24% in the LD protocol, respectively. CONCLUSIONS: Our study highlights the necessity for reconsidering radiation dose protocols in neurointerventional procedures, especially at the level of baseline factory settings.

Preoperative Use of CT Angiography in Infants With Coarctation of the Aorta.

BACKGROUND: Computed tomographic angiography (CTA) and echocardiography (echo) are used preoperatively in coarctation of the aorta to define arch hypoplasia and great vessel branching. We sought to determine differences in quantitative measurements, as well as surgical utility, between modalities. METHODS: Infants (less than six months) with both CTA and echo prior to coarctation repair from 2004 to 2013 were included. Measurements were compared and correlated with surgical approach. Three surgeons reviewed de-identified images to predict approach and characterize utility. Computed tomographic angiography radiation dose was calculated. RESULTS: Thirty-three patients were included. No differences existed in arch measurements between echo and CTA ( z-score: -2.59 vs -2.43; P = .47). No differences between modalities were seen for thoracotomy ( z-score: -2.48 [echo] vs -2.31 [CTA]; P = .48) or sternotomy ( z-score: -3.13 [echo] vs -3.08 [CTA]; P = .84). Computed tomographic angiography delineated great vessel branching pattern in two patients with equivocal echo findings ( P = .60). Surgeons rated CTA as far more useful than echo in understanding arch hypoplasia and great vessel branching in cases where CTA was done to resolve anatomical questions that remain after echo evaluation. Two of three surgeons were more likely to choose the surgical approach taken based on CTA (surgeon A, P = .02; surgeon B, P = .01). Radiation dose averaged 2.5 (1.6) mSv and trended down from 2.9 mSv (1.8 mSv; n = 20) to 1.6 mSv (0.5 mSv; n = 7) ( P = .06) with new technology. CONCLUSION: Although CTA and echo measurements of the aorta do not differ, CTA better delineates branching and surgeons strongly prefer it for three-dimensional arch anatomy. We recommend CTA for patients with anomalous arch branching patterns, diffuse or complex hypoplasia, or unusual arch morphology not fully elucidated by echo.

Monitoring change in volume of calcifications in juvenile idiopathic inflammatory myopathy: a pilot study using low dose computed tomography.

BACKGROUND: Dystrophic calcifications may occur in patients with J uvenile Idiopathic Inflammatory Myopathy (JIIM) as well as other connective tissue and metabolic diseases, but a reliable method of measuring the volume of these calcifications has not been established. The purpose of this study is to determine the feasibility of low dose, limited slice, Computed Tomography (CT) to measure objectively in-situ calcification volumes in patients with JIIM over time. METHODS: Ten JIIM patients (eight JDM, two Overlap) with calcifications were prospectively recruited over a 2-year period to undergo two limited, low dose, four-slice CT scans. Calculation of the volume of calcifications used a CT post processing workstation. Additional patient data included: Disease Activity Scores (DAS), Childhood Myositis Assessment Scale (CMAS), myositis specific antibodies (MSA), and the TNFα-308 promoter region A/G polymorphism. Statistical analysis utilized the Pearson correlation coefficient, the paired t-test and descriptive statistics. RESULTS: Ten JIIM, mean age 14.54 ± 4.54 years, had a duration of untreated disease of 8.68 ± 5.65 months  MSA status: U1RNP (1), PM-Scl (1), Ro (1, 4 indeterminate), p155/140 (2), MJ (3), Mi-2 indeterminate (1), negative (3). 4/8 JDM (50%) were TNF-α-308 A+. Overall, the calcification volumes tended to decrease from the first to the second CT study by 0.5 cm3 (from 2.79 ± 1.98 cm3 to 2.29 ± 2.25 cm3). The average effective radiation dose was 0.007 ± 0.002, 0.010 ± 0.005, and 0.245 mSv for the upper extremity, lower extremity and chest, respectively (compared to a standard chest x-ray-- 0.02mSV effective dosage). CONCLUSION: We conclude: 1) the limited low dose CT technique provides objective data about volume of the calcifications in JIIM; 2) measuring the volume of calcifications in an extremity is associated with minimal radiation exposure; 3) This method may be useful to evaluate the efficacy of therapies for JIIM dystrophic calcification.

Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate.

AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer. METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy. RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum. CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.

Validation of optimal DCE-MRI perfusion threshold to classify at-risk tumor imaging voxels in heterogeneous cervical cancer for outcome prediction.

PURPOSE: To classify tumor imaging voxels at-risk for treatment failure within the heterogeneous cervical cancer using DCE MRI and determine optimal voxel's DCE threshold values at different treatment time points for early prediction of treatment failure. MATERIAL AND METHOD: DCE-MRI from 102 patients with stage IB2-IVB cervical cancer was obtained at 3 different treatment time points: before (MRI 1) and during treatment (MRI 2 at 2-2.5 weeks and MRI 3 at 4-5 weeks). For each tumor voxel, the plateau signal intensity (SI) was derived from its time-SI curve from the DCE MRI. The optimal SI thresholds to classify the at-risk tumor voxels was determined by the maximal area under the curve using ROC analysis when varies SI value from 1.0 to 3.0 and correlates with treatment outcome. RESULTS: The optimal SI thresholds for MRI 1, 2 and 3 were 2.2, 2.2 and 2.1 for significant differentiation between local recurrence/control, respectively, and 1.8, 2.1 and 2.2 for death/survival, respectively. CONCLUSION: Optimal SI thresholds are clinically validated to quantify at-risk tumor voxels which vary with time. A single universal threshold (SI=1.9) was identified for all 3 treatment time points and remained significant for the early prediction of treatment failure.

Transient lesion in the splenium of the corpus callosum in acute uncomplicated falciparum malaria.

Patients with acute uncomplicated Plasmodium falciparum malaria have no evident neurologic disorder, vital organ dysfunction, or other severe manifestations of infection. Nonetheless, parasitized erythrocytes cytoadhere to the endothelium throughout their microvasculature, especially within the brain. We aimed to determine if 3 Tesla magnetic resonance imaging studies could detect evidence of cerebral abnormalities in these patients. Within 24 hours of admission, initial magnetic resonance imaging examinations found a lesion with restricted water diffusion in the mid-portion of the splenium of the corpus callosum of 4 (40%) of 10 male patients. The four patients who had a splenial lesion initially had evidence of more severe hemolysis and thrombocytopenia than the six patients who had no apparent abnormality. Repeat studies four weeks later found no residua of the lesions and resolution of the hematologic differences. These observations provide evidence for acute cerebral injury in the absence of severe or cerebral malaria.

RF-related heating assessment of extracranial neurosurgical implants at 7T.

PURPOSE: The purpose was to evaluate radiofrequency (RF)-related heating of commonly used extracranial neurosurgical implants in 7-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Experiments were performed using a 7-T MR system equipped with a transmit/receive RF head coil. Four commonly used titanium neurosurgical implants were studied using a test procedure adapted from the American Society for Testing and Materials Standard F2182-11a. Implants (n=4) were tested with an MRI turbo spin echo pulse sequence designed to achieve maximum RF exposure [specific absorption rate (SAR) level=9.9W/kg], which was further validated by performing calorimetry. Maximum temperature increases near each implant's surface were measured using fiberoptic temperature probes in a gelled-saline-filled phantom that mimicked the conductive properties of soft tissue. Measurement results were compared to literature data for patient safety. RESULTS: The highest achievable phantom averaged SAR was determined by calorimetry to be 2.0±0.1W/kg due to the highly conservative SAR estimation model used by this 7-T MR system. The maximum temperature increase at this SAR level was below 1.0°C for all extracranial neurosurgical implants that underwent testing. CONCLUSION: The findings indicated that RF-related heating under the conditions used in this investigation is not a significant safety concern for patients with the particular extracranial neurosurgical implants evaluated in this study.

Measurement and correction of stimulated echo contamination in T2-based iron quantification.

The purpose of this study was to characterize the effects of stimulated echo contamination on MR-based iron measurement derived from quantitative T2 images and develop a method for retrospective correction. Two multiple spin-echo (MSE) pulse sequences were implemented with different amounts of stimulated echo contamination. Agarose-based phantoms were constructed that simulate the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron. Additionally, myocardial iron was assessed in nine human subjects with transfusion iron overload. These data were used to determine the influence of stimulated echoes on iron measurements made by an MR-based iron quantification model that can separately measure dispersed and aggregated iron. The study found that stimulated echo contamination caused an underestimation of dispersed (ferritin-like) iron and an overestimation of aggregated (hemosiderin-like) iron when applying this model. The relationship between the measurements made with and without stimulated echo appears to be linear. The findings suggest that while it is important to use MSE sequences with minimal stimulated echo in T2-based iron quantification, it appears that data acquired with sub-optimal sequences can be retrospectively corrected using the methodology described here.

Structural brain alterations can be detected early in HIV infection.

OBJECTIVE: Brain changes occurring early in HIV infection are not well characterized. The Chicago Early HIV Infection Study aimed to evaluate the presence and extent of structural brain alterations using quantitative MRI. METHODS: Forty-three HIV and 21 control subjects were enrolled. Mean length of infection was estimated as less than 1 year based on assay results. High-resolution neuroanatomical images were acquired. Automated image analysis was used to derive measurements for total brain, ventricular volume, and for tissue classes (total and cortical gray matter, white matter, and CSF). A separate image analysis algorithm was used to calculate measurements for individual brain regions. Cognitive function was assessed by neuropsychological evaluation. RESULTS: Reductions were quantified in total (p = 0.0547) and cortical (p = 0.0109) gray matter in the HIV group. Analysis of individual brain regions with a separate image analysis algorithm revealed consistent findings of reductions in cerebral cortex (p = 0.042) and expansion of third ventricle (p = 0.046). The early HIV group also demonstrated weaker performance on several neuropsychological tests, with the most pronounced difference in psychomotor speed (p = 0.001). CONCLUSIONS: This cross-sectional brain volumetric study indicates structural alterations early in HIV infection. The findings challenge the prevailing assumption that the brain is spared in this period. Revisiting the question of the brain's vulnerability to processes unfolding in the initial virus-host interaction and the early natural history may yield new insights into neurologic injury in HIV infection and inform neuroprotection strategies.

Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.

The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T.

Characterizing tumor heterogeneity with functional imaging and quantifying high-risk tumor volume for early prediction of treatment outcome: cervical cancer as a model.

PURPOSE: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. METHODS AND MATERIALS: DCE-MRI was performed in 102 stage IB(2)-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). RESULTS: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm(3), respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10(-8), 2.0 × 10(-8)) and disease-specific survival (p = 1.9 × 10(-4), 2.1 × 10(-6), 2.5 × 10(-7), respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. DISCUSSION: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2-5 weeks into treatment.