Is a Close Follow-Up Computed Tomography Necessary for Acute Falcine and Tentorial Subdural Hematoma?

OBJECTIVE: This study aimed to assess the changes and values on follow-up computed tomography (F/U-CT) for isolated falcine (F-SDH) and tentorial (T-SDH) subdural hematomas (SDHs). METHOD: Fifty-four cases of isolated F-SDH and/or T-SDH were retrospectively reviewed. Subdural hematoma morphology, mass effect on the adjacent parenchyma, and interval change at F/U-CT were evaluated. Subdural hematoma size was measured parallel and perpendicular to the falx/tentorium (long or short axis, respectively). RESULTS: Short-axis increase on F/U-CT was seen only in 5 F-SDHs (16%) and 7 T-SDHs (19%), with a maximum of a 2-mm increase. Long-axis growth was more prominent and frequent, seen in 18 F-SDH patients (56.2%) and 19 T-SDH patients (51.4%), with maximum change of up to 43 mm. Falcine SDH and T-SDH were ipsilateral and contiguous in 77.8% of patients. Minimal mass effect was seen in 13 patients (24.1%), which was resolved or stable on F/U-CT. Anticoagulation did not affect SDH size. No patients required neurosurgery or died. CONCLUSIONS: Based on our limited data, the current standard of F/U-CT may be unnecessary in patients with isolated F-SDH and/or T-SDH, which expand minimally along the short axis without a significant mass effect. Characteristic anatomic structure of the tentorium and falx, and their connectivity may direct SDH expansion and limit mass effect as well as injury to the adjacent parenchyma.

Whole-Lesion DCE-MRI Intensity Histogram Analysis for Diagnosis in Patients with Suspected Lung Cancer.

RATIONALE AND OBJECTIVES: To explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) intensity histogram metrics, relative to time intensity curve (TIC)-derived metrics, in patients with suspected lung cancer. MATERIALS AND METHODS: This retrospective study enrolled 49 patients with suspected lung cancer on routine CT imaging who underwent DCE-MRI scans and had final histopathologic diagnosis. Three TIC-derived metrics (maximum enhancement ratio, peak time [Tmax] and slope) and eight intensity histogram metrics (volume, integral, maximum, minimum, median, coefficient of variation [CoV], skewness, and kurtosis) were extracted from DCE-MRI images. TIC-derived and intensity histogram metrics were compared between benignity versus malignancy using the Wilcoxon rank-sum test. Associations between imaging metrics and malignancy risk were assessed by univariate and multivariate logistic regression odds ratios (ORs). RESULTS: There were 33 malignant lesions and 16 benign lesions based on histopathology. Lower CoV (OR = 0.2 per 1-SD increase, p = 0.0006), lower Tmax (OR = 0.4 per 1-SD increase, p = 0.005), and steeper slope (OR = 2.4 per 1-SD increase, p = 0.010) were significantly associated with increased risk of malignancy. Under multivariate analysis, CoV was significantly independently associated with malignancy likelihood after accounting for either Tmax (OR = 0.3 per 1-SD increase, p = 0.007) or slope (OR = 0.3 per 1-SD increase, p = 0.011). CONCLUSION: This initial study found that DCE-MRI CoV was independently associated with malignancy in patients with suspected lung cancer. CoV has the potential to help diagnose indeterminate pulmonary lesions and may complement TIC-derived DCE-MRI metrics. Further studies are warranted to validate the diagnostic value of DCE-MRI intensity histogram analysis.

The Dancing Cord: Inherent Spinal Cord Motion and Its Effect on Cord Dose in Spine Stereotactic Body Radiation Therapy.

BACKGROUND: Spinal cord dose limits are critically important for the safe practice of spine stereotactic body radiotherapy (SBRT). However, the effect of inherent spinal cord motion on cord dose in SBRT is unknown. OBJECTIVE: To assess the effects of cord motion on spinal cord dose in SBRT. METHODS: Dynamic balanced fast field echo (BFFE) magnetic resonance imaging (MRI) was obtained in 21 spine metastasis patients treated with SBRT. Planning computed tomography (CT), conventional static T2-weighted MRI, BFFE MRI, and dose planning data were coregistered. Spinal cord from the dynamic BFFE images (corddyn) was compared with the T2-weighted MRI (cordstat) to analyze motion of corddyn beyond the cordstat (Dice coefficient, Jaccard index), and beyond cordstat with added planning organ at risk volume (PRV) margins. Cord dose was compared between cordstat, and corddyn (Wilcoxon signed-rank test). RESULTS: Dice coefficient (0.70-0.95, median 0.87) and Jaccard index (0.54-0.90, median 0.77) demonstrated motion of corddyn beyond cordstat. In 62% of the patients (13/21), the dose to corddyn exceeded that of cordstat by 0.6% to 13.8% (median 4.3%). The corddyn spatially excursed outside the 1-mm PRV margin of cordstat in 9 patients (43%); among these dose to corddyn exceeded dose to cordstat >+ 1-mm PRV margin in 78% of the patients (7/9). Corddyn did not excurse outside the 1.5-mm or 2-mm PRV cord cordstat margin. CONCLUSION: Spinal cord motion may contribute to increases in radiation dose to the cord from SBRT for spine metastasis. A PRV margin of at least 1.5 to 2 mm surrounding the cord should be strongly considered to account for inherent spinal cord motion.

Strategies to Mitigate Toxicities From Stereotactic Body Radiation Therapy for Spine Metastases.

Improvements in systemic therapy are translating into more patients living longer with metastatic disease. Bone is the most common site of metastasis, where spinal lesions can result in significant pain impacting quality of life and possible neurological dysfunction resulting in a decline in performance status. Stereotactic body radiation therapy (SBRT) of the spine has emerged as a promising technique to provide durable local control, palliation of symptoms, control of oligoprogressive sites of disease, and possibly augment the immune response. SBRT achieves this by delivering highly conformal radiation therapy to allow for dose escalation due to a steep dose gradient from the planning target volume to nearby critical organs at risk. In our review, we provide an in-depth review and expert commentary regarding seminal literature that defined clinically meaningful toxicity endpoints with actionable dosimetric limits and/or clinical management strategies to mitigate toxicity potentially attributable to SBRT of the spine. We placed a spotlight on radiation myelopathy (de novo, reirradiation after conventional external beam radiation therapy or salvage after an initial course of spinal SBRT), plexopathy, vertebral compression fracture, pain flare, esophageal toxicity, myositis, and safety regarding combination with concurrent targeted or immune therapies.

Neuroimaging for Radiation Therapy of Brain Tumors.

Delineating the gross tumor volume (GTV) is a core task within radiation treatment planning. GTVs must be precisely defined irrespective of the region involved, but even more so in a sensitive area such as the brain. As precision medicine cannot exist without precision imaging, the current article aims to discuss the various imaging modalities employed in the radiation treatment planning of brain tumors.Gliomas, meningiomas, and paragangliomas are some of the most challenging tumors and the advancement in diagnostic imaging can significantly contribute to their delineation. For gliomas, irradiation based on multiparametric magnetic resonance imaging (MRI) and amino-acid positron emission tomography (PET)/computed tomography (CT) may have a higher sensitivity and specificity, which could lead to a better sparing of organs at risk and help distinguish between tumor, edema, and radiogenic alterations. Meningiomas and paragangliomas are often associated with a good prognosis. Therefore, GTV delineation according to MRI and somatostatin receptor ligand-PET/CT plays an essential role in sparing sensitive structures and maintaining a good quality of life for these patients.The combination of multiparametric MRI and PET/CT (possibly in the form of PET/MRI) presently appears to be the optimal approach for target volume delineation. The comparative efficacy of these imaging modalities has to be further evaluated in prospective trials.

Diffusion-weighted MRI and ADC versus FET-PET and GdT1w-MRI for gross tumor volume (GTV) delineation in re-irradiation of recurrent glioblastoma.

BACKGROUND AND PURPOSE: GTV definition for re-irradiation treatment planning in recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w-MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for active tumor. The objective of this study was to compare the localization and quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and GdT1w-MRI (GTV-GdT1w-MRI). MATERIAL AND METHODS: We prospectively evaluated 41 patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV-PET was generated automatically (tumor-to-background ratio 1.7-1.8) and manually customized. GTV-ADClow was manually defined based on DWI data (3D diffusion gradients, b = 0, 1000 s/mm2) and parametric ADC maps. The localization of recurrence was correlated with initial GdT1w-MRI and PET data. RESULTS: In 30/41 patients, DWI-MRI showed areas with restricted diffusion (mean ADC-value 0.74 ±â€¯0.22 mm2/s). 66% of GTVs-ADClow were located outside the GdT1w-MRI volume and 76% outside increased FET uptake regions. Furthermore, GTVs-ADClow were only partially included in the high dose volume and received in mean 82% of the reference dose. An adjusted volume including GdT1w-MRI, PET-positive and restricted diffusion areas would imply a GTV increase of 48%. GTV-PET and GdT1w-MRI correlated better with the localization of re-recurrence in comparison to GTV-ADClow. CONCLUSION: Unexpectedly, GTV-ADClow overlapped only partially with FET-PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM-recurrences. Seeing as a restricted diffusion is known to correlate with hypercellularity, this imaging discrepancy could only be further explained in histopathological studies.

Tumor radiomic heterogeneity: Multiparametric functional imaging to characterize variability and predict response following cervical cancer radiation therapy.

BACKGROUND: Robust approaches to quantify tumor heterogeneity are needed to provide early decision support for precise individualized therapy. PURPOSE: To conduct a technical exploration of longitudinal changes in tumor heterogeneity patterns on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and FDG positron emission tomography / computed tomography (PET/CT), and their association to radiation therapy (RT) response in cervical cancer. STUDY TYPE: Prospective observational study with longitudinal MRI and PET/CT pre-RT, early-RT (2 weeks), and mid-RT (5 weeks). POPULATION: Twenty-one FIGO IB2 -IVA cervical cancer patients receiving definitive external beam RT and brachytherapy. FIELD STRENGTH/SEQUENCE: 1.5T, precontrast axial T1 -weighted, axial and sagittal T2 -weighted, sagittal DWI (multi-b values), sagittal DCE MRI (<10 sec temporal resolution), postcontrast axial T1 -weighted. ASSESSMENT: Response assessment 1 month after completion of treatment by a board-certified radiation oncologist from manually delineated tumor volume changes. STATISTICAL TESTS: Intensity histogram (IH) quantiles (DCE SI10% and DWI ADC10% , FDG-PET SUVmax ) and distribution moments (mean, variance, skewness, kurtosis) were extracted. Differences in IH features between timepoints and modalities were evaluated by Skillings-Mack tests with Holm's correction. Area under receiver-operating characteristic curve (AUC) and Mann-Whitney testing was performed to discriminate treatment response using IH features. RESULTS: Tumor IH means and quantiles varied significantly during RT (SUVmean : ↓28-47%, SUVmax : ↓30-59%, SImean : ↑8-30%, SI10% : ↑8-19%, ADCmean : ↑16%, P < 0.02 for each). Among IH heterogeneity features, FDG-PET SUVCoV (↓16-30%, P = 0.011) and DW-MRI ADCskewness decreased (P = 0.001). FDG-PET SUVCoV was higher than DCE-MRI SICoV and DW-MRI ADCCoV at baseline (P < 0.001) and 2 weeks (P = 0.010). FDG-PET SUVkurtosis was lower than DCE-MRI SIkurtosis and DW-MRI ADCkurtosis at baseline (P = 0.001). Some IH features appeared to associate with favorable tumor response, including large early RT changes in DW-MRI ADCskewness (AUC = 0.86). DATA CONCLUSION: Preliminary findings show tumor heterogeneity was variable between patients, modalities, and timepoints. Radiomic assessment of changing tumor heterogeneity has the potential to personalize treatment and power outcome prediction. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1388-1396.

Intravoxel incoherent motion MRI assessment of chemoradiation-induced pelvic bone marrow changes in cervical cancer and correlation with hematological toxicity.

PURPOSE: To investigate bone marrow changes after chemoradiation (CRT) using intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) and correlate imaging changes with hematological toxicity (HT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: Thirty-nine patients with newly diagnosed cervical cancer were prospectively recruited for two sequential 3.0T IVIM-MRI studies: before treatment (MRI-1) and 3-4 weeks after standardized CRT (MRI-2). The irradiated pelvic bone marrow was outlined as the regions of interest to derive the true diffusion coefficient (D) and perfusion fraction (f) based on a biexponential model. The apparent coefficient diffusion (ADC) was derived using the monoexponential model. Changes in these parameters between MRI-1 and MRI-2 were calculated as ΔD, Δf, and ΔADC. HT was defined accordingly to NCI-CTCAE (v. 4.03) of grade 3 and above. Statistical analysis was performed using Mann-Whitney U-test. RESULTS: The median age of patients was 54 years old (range 27-83 years old); 14 patients suffered from HT. Early bone marrow changes (3-4 weeks) of ΔD showed a significant difference between HT and non-HT groups (6.4 ± 19.7% vs. -6.4 ± 19.4%, respectively, P = 0.041). However, no significant changes were noted in Δf (3.7 ± 13.3% vs. 1.5 ± 12.5% respectively, P = 0. 592) and ΔADC (5.5 ± 26.3% vs. -3.3 ± 27.0% respectively, P = 0.303) between the HT and non-HT groups. Δf increased insignificantly for both groups. CONCLUSION: ΔD was the only significant parameter to differentiate early cellular environment changes in bone marrow after CRT, suggestive that ΔD was more sensitive than Δf and ΔADC to reflect the underlying microenvironment injury. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1491-1498.

Revisiting Current Golden Rules in Managing Acute Ischemic Stroke: Evaluation of New Strategies to Further Improve Treatment Selection and Outcome.

OBJECTIVE: Advanced stroke imaging has generated much excitement for the early diagnosis of acute ischemic stroke (AIS) and facilitation of intervention. However, its therapeutic impact has not matched its diagnostic utility; most notably, lacking significant contributions to recent major AIS clinical trials. It is time to reexamine the fundamental hypotheses from the enormous body of imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS. In this article, we will investigate a possible new window of opportunity in managing AIS through a better understanding of the following: first, the potential limitations of the golden rules; second, the significance of imaging-based parenchymal hypoperfusion (i.e., lower-than-normal relative cerebral blood flow [rCBF] may not be indicative of ischemia); third, the other critical factors (e.g., rCBF, collateral circulation, variable therapeutic window, chronicity of occlusion) that reflect more individual ischemic injury for optimal treatment selection; and, fourth, the need for penumbra validation in successfully reperfused patients (not in untreated patients). CONCLUSION: Individual variations in the therapeutic window, ischemic injury (rCBF), and chronicity of vascular lesion development have not been comprehensively incorporated in the standard algorithms used to manage AIS. The current established imaging parameters have not been consistently validated with successfully reperfused patients and rCBF to quantitatively distinguish between oligemia and ischemia and between penumbra and infarct core within ischemic tissue. A novel paradigm incorporating rCBF values or indirectly incorporating relative rCBF values with higher statistically powered imaging studies to more reliably assess the severity of ischemic injury and differentiate reversibility from viability within the area of imaging-based parenchymal hypoperfusion may provide a more personalized approach to treatment, including no treatment of infarction core, to further enhance outcomes.

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.

Imaging across the life span: innovations in imaging and therapy for gynecologic cancer.

The focus of this article is radiation therapy for gynecologic cancers, with emphasis on imaging-based treatment planning and delivery. For the various gynecologic cancers, radiation oncologists rely on essential clinical information to triage treatment options, and various imaging studies are performed for treatment planning and radiation therapy delivery. A practical approach is provided to help radiologists tailor their reports for the needs of their radiation oncology and gynecologic oncology colleagues, to optimize multidisciplinary care for patients with gynecologic cancer. Template radiology reports are proposed to address the specific information needs of oncologists at each phase-before, during, and after treatment. Fueled by the rapid progress in engineering and computer sciences during the past 2 decades, remarkable advances have been made in anatomic, functional, and molecular imaging and in radiation treatment planning and delivery in patients with gynecologic cancer. Radiation therapy has evolved from a nontargeted approach to a precisely targeted, highly conformal treatment modality, to further improve treatment outcomes and reduce morbidity. High-quality imaging has become essential for staging of the disease, delineation of tumor extent for treatment planning and delivery, and monitoring therapy response. Anatomic and functional imaging has also been shown to provide prognostic information that allows clinicians to tailor therapy on the basis of personalized patient information. This field is an area of active research, and future clinical trials are warranted to validate preliminary results in the field.

Understanding patient satisfaction ratings for radiology services.

OBJECTIVE: Under the Hospital Value-Based Purchasing Program of the Centers for Medicare & Medicaid Services, patient satisfaction accounts for 30% of the measures of and payments for quality of care. Understanding what drives patient satisfaction data and how the data are obtained, converted into scores, and formulated into rankings is increasingly critical for imaging departments. The objectives of this article are to describe the potential impact of patient satisfaction ratings on institutions and individuals, explain how patient satisfaction is rated and ranked, identify drivers that affect the ratings and rankings, and probe the resulting challenges unique to radiology departments. CONCLUSION: Research results indicate that training providers to make simple modifications in their language and behavior during patient care can significantly impact patient satisfaction, which, in turn, can impact both quality-of-care ratings and the bottom line of hospitals. Training providers is a simple and cost-effective way to potentiate the clinical expression of compassion into improvement of patient satisfaction and financial reward, a national trend that no one in the game can afford to ignore.

Unusual motion detected on real-time sonography inside a glomus tumor in the thigh.

Glomus tumors are rare and many have been reported to have a hypervascular appearance on color or power Doppler sonography. We report a pathologically proven case of superficial glomus tumor within the thigh with no detectable color flow signals on color or power Doppler sonography. In addition, real-time sonography showed spontaneous motions within the tumor, which were not synchronized with vascular or respiratory motions, and misled the presurgical diagnosis of a suspected parasite in a patient who had direct contact with multiple animal species. The etiology of this internal motion remains hypothetical but, if reconfirmed, this finding may be a useful adjunctive sign for the diagnosis of glomus tumors.

"Tumoral pseudoblush" identified within gliomas at high-spatial-resolution ultrahigh-field-strength gradient-echo MR imaging corresponds to microvascularity at stereotactic biopsy.

PURPOSE: To use directed biopsy sampling to determine whether microvascular assessment within gliomas, by means of ultrahigh-field-strength high-spatial-resolution gradient-echo (GRE) magnetic resonance (MR) imaging at 8 T, correlates with histopathologic assessment of microvascularity. MATERIALS AND METHODS: The study was institutional review board approved and HIPAA compliant. Informed consent was obtained. Thirty-five subjects with gliomas underwent 8-T and 80-cm MR imaging by using a GRE sequence (repetition time, 600-750 msec; echo time, 10 msec; in-plane resolution, 196 mm). Haphazardly arranged serpentine low-signal-intensity structures, often associated with areas of low signal intensity within the tumor bed ("tumoral pseudoblush") at MR imaging, were presumed to be related to tumoral microvascularity. Microvessel density (MVD) and microvessel size (MVS) ranked with a semiquantitative three-tier scale (high, medium, and low) relative to cortical penetrating veins were assessed from regions of interest identified at MR imaging and were compared with a similar assessment of stereotactic biopsy specimens by using Kendall τb. Tumor grade (high vs low) was compared with ultrahigh-field-strength high-resolution GRE MR analysis by using Pearson χ2. Discrepancies between 8-T and histopathologic assessment were identified and analyzed. RESULTS: Ultrahigh-field-strength high-resolution GRE MR imaging and histopathologic assessment concurred for MVS (P<.0001) and MVD (P<.0001). World Health Organization classification tumor grade was associated with number (P<.0005) and size (P<.0005) of foci of microvascularity within the tumor bed at 8-T MR imaging. Radiation-induced microvessel hyalinosis mimicked tumor microvascularity at 8-T MR imaging. Potential confounders could result from radiofrequency inhomogeneity and displaced normal microvasculature. CONCLUSION: Microvascularity identified as a tumoral pseudoblush at ultrahigh-field-strength high-resolution GRE MR imaging without contrast material shows promise as a marker for increased tumoral microvascularity.

Onset time of tumor repopulation for cervical cancer: first evidence from clinical data.

PURPOSE: Accelerated tumor repopulation has significant implications in low-dose rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer, using clinical data. METHODS AND MATERIALS: The linear quadratic (LQ) model extended for tumor repopulation was used to analyze clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ(2) method was used to fit the TCP data with two free parameters: onset time (T(k)) of accelerated repopulation and number of clonogens (K), while other LQ model parameters were adopted from the literature, due to the limited patient data. RESULTS: Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated with higher TCP. Using the LQ model, we achieved the best fit with onset time T(k) of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T(k) and (48, 1822) for K, respectively. CONCLUSION: This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.

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.