Evolutionary Strategies Enable Systematic and Reliable Uncertainty Quantification: A Proof-of-Concept Pilot Study on Resting-State Functional MRI Language Lateralization.

Reliable and trustworthy artificial intelligence (AI), particularly in high-stake medical diagnoses, necessitates effective uncertainty quantification (UQ). Existing UQ methods using model ensembles often introduce invalid variability or computational complexity, rendering them impractical and ineffective in clinical workflow. We propose a UQ approach based on deep neuroevolution (DNE), a data-efficient optimization strategy. Our goal is to replicate trends observed in expert-based UQ. We focused on language lateralization maps from resting-state functional MRI (rs-fMRI). Fifty rs-fMRI maps were divided into training/testing (30:20) sets, representing two labels: "left-dominant" and "co-dominant." DNE facilitated acquiring an ensemble of 100 models with high training and testing set accuracy. Model uncertainty was derived from distribution entropies over the 100 model predictions. Expert reviewers provided user-based uncertainties for comparison. Model (epistemic) and user-based (aleatoric) uncertainties were consistent in the independently and identically distributed (IID) testing set, mainly indicating low uncertainty. In a mostly out-of-distribution (OOD) holdout set, both model and user-based entropies correlated but displayed a bimodal distribution, with one peak representing low and another high uncertainty. We also found a statistically significant positive correlation between epistemic and aleatoric uncertainties. DNE-based UQ effectively mirrored user-based uncertainties, particularly highlighting increased uncertainty in OOD images. We conclude that DNE-based UQ correlates with expert assessments, making it reliable for our use case and potentially for other radiology applications.

Differentiating Low-Grade from High-Grade Intracranial Ependymomas: Comparison of Dynamic Contrast-Enhanced MRI and Diffusion-Weighted Imaging.

BACKGROUND AND PURPOSE: The aim of this study was to determine the diagnostic value of fractional plasma volume derived from dynamic contrast-enhanced perfusion MR imaging versus ADC, obtained from DWI in differentiating between grade 2 (low-grade) and grade 3 (high-grade) intracranial ependymomas. MATERIALS AND METHODS: A hospital database was created for the period from January 2013 through June 2022, including patients with histologically-proved ependymoma diagnosis with available dynamic contrast-enhanced MR imaging. Both dynamic contrast-enhanced perfusion and DWI were performed on each patient using 1.5T and 3T scanners. Fractional plasma volume maps and ADC maps were calculated. ROIs were defined by a senior neuroradiologist manually by including the enhancing tumor on every section and conforming a VOI to obtain the maximum value of fractional plasma volume (Vpmax) and the minimum value of ADC (ADCmin). A Mann-Whitney U test at a significance level of corrected P = .01 was used to evaluate the differences. Additionally, receiver operating characteristic curve analysis was applied to assess the sensitivity and specificity of Vpmax and ADCmin values. RESULTS: A total of 20 patients with ependymomas (10 grade 2 tumors and 10 grade 3 tumors) were included. Vpmax values for grade 3 ependymomas were significantly higher (P < .002) than those for grade 2. ADCmin values were overall lower in high-grade lesions. However, no statistically significant differences were found (P = .12114). CONCLUSIONS: As a dynamic contrast-enhanced perfusion MR imaging metric, fractional plasma volume can be used as an indicator to differentiate grade 2 and grade 3 ependymomas. Dynamic contrast-enhanced perfusion MR imaging plays an important role with high diagnostic value in differentiating low- and high-grade ependymoma.

Longitudinal Evaluation of DCE-MRI as an Early Indicator of Progression after Standard Therapy in Glioblastoma.

Background and Purpose: Distinguishing treatment-induced imaging changes from progressive disease has important implications for avoiding inappropriate discontinuation of a treatment. Our goal in this study is to evaluate the utility of dynamic contrast-enhanced (DCE) perfusion MRI as a biomarker for the early detection of progression. We hypothesize that DCE-MRI may have the potential as an early predictor for the progression of disease in GBM patients when compared to the current standard of conventional MRI. Methods: We identified 26 patients from 2011 to 2023 with newly diagnosed primary glioblastoma by histopathology and gross or subtotal resection of the tumor. Then, we classified them into two groups: patients with progression of disease (POD) confirmed by pathology or change in chemotherapy and patients with stable disease without evidence of progression or need for therapy change. Finally, at least three DCE-MRI scans were performed prior to POD for the progression cohort, and three consecutive DCE-MRI scans were performed for those with stable disease. The volume of interest (VOI) was delineated by a neuroradiologist to measure the maximum values for Ktrans and plasma volume (Vp). A Friedman test was conducted to evaluate the statistical significance of the parameter changes between scans. Results: The mean interval between subsequent scans was 57.94 days, with POD-1 representing the first scan prior to POD and POD-3 representing the third scan. The normalized maximum Vp values for POD-3, POD-2, and POD-1 are 1.40, 1.86, and 3.24, respectively (FS = 18.00, p = 0.0001). It demonstrates that Vp max values are progressively increasing in the three scans prior to POD when measured by routine MRI scans. The normalized maximum Ktrans values for POD-1, POD-2, and POD-3 are 0.51, 0.09, and 0.51, respectively (FS = 1.13, p < 0.57). Conclusions: Our analysis of the longitudinal scans leading up to POD significantly correlated with increasing plasma volume (Vp). A longitudinal study for tumor perfusion change demonstrated that DCE perfusion could be utilized as an early predictor of tumor progression.

T1-Weighted, Dynamic Contrast-Enhanced MR Perfusion Imaging Can Differentiate between Treatment Success and Failure in Spine Metastases Undergoing Radiation Therapy.

BACKGROUND AND PURPOSE: Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure. MATERIALS AND METHODS: This retrospective study included 49 patients (mean age, 63 [SD, 13] years; 29 men) with metastatic lesions treated with radiation therapy who underwent dynamic contrast-enhanced MR imaging. The median time between radiation therapy and follow-up dynamic contrast-enhanced MR imaging was 62 days. We divided patients into 2 groups: clinical success (n = 38) and failure (n = 11). Failure was defined as PET recurrence (n = 5), biopsy-proved (n = 1) recurrence, or an increase in tumor size (n = 7), while their absence defined clinical success. A Mann-Whitney U test was performed to assess differences between groups. RESULTS: The reduction in plasma volume was greater in the success group than in the failure group (-57.3% versus +88.2%, respectively; P < .001). When we assessed the success of treatment, the sensitivity of plasma volume was 91% (10 of 11; 95% CI, 82%-97%) and the specificity was 87% (33 of 38; 95% CI, 73%-94%). The sensitivity of size measurements was 82% (9 of 11; 95% CI, 67%-90%) and the specificity was 47% (18 of 38; 95% CI, 37%-67%). CONCLUSIONS: The specificity of plasma volume was higher than that of conventional size measurements, suggesting that dynamic contrast-enhanced MR imaging is a powerful tool to discriminate between treatment success and failure.

Delay of Aortic Arterial Input Function Time Improves Detection of Malignant Vertebral Body Lesions on Dynamic Contrast-Enhanced MRI Perfusion.

Dynamic contrast-enhanced MRI (DCE) is an emerging modality in the study of vertebral body malignancies. DCE-MRI analysis relies on a pharmacokinetic model, which assumes that contrast uptake is simultaneous in the feeding of arteries and tissues of interest. While true in the highly vascularized brain, the perfusion of the spine is delayed. This delay of contrast reaching vertebral body lesions can affect DCE-MRI analyses, leading to misdiagnosis for the presence of active malignancy in the bone marrow. To overcome the limitation of delayed contrast arrival to vertebral body lesions, we shifted the arterial input function (AIF) curve over a series of phases and recalculated the plasma volume values (Vp) for each phase shift. We hypothesized that shifting the AIF tracer curve would better reflect actual contrast perfusion, thereby improving the accuracy of Vp maps in metastases. We evaluated 18 biopsy-proven vertebral body metastases in which standard DCE-MRI analysis failed to demonstrate the expected increase in Vp. We manually delayed the AIF curve for multiple phases, defined as the scan-specific phase temporal resolution, and analyzed DCE-MRI parameters with the new AIF curves. All patients were found to require at least one phase-shift delay in the calculated AIF to better visualize metastatic spinal lesions and improve quantitation of Vp. Average normalized Vp values were 1.78 ± 1.88 for zero phase shifts (P0), 4.72 ± 4.31 for one phase shift (P1), and 5.59 ± 4.41 for two phase shifts (P2). Mann-Whitney U tests obtained p-values = 0.003 between P0 and P1, and 0.0004 between P0 and P2. This study demonstrates that image processing analysis for DCE-MRI in patients with spinal metastases requires a careful review of signal intensity curve, as well as a possible adjustment of the phase of aortic AIF to increase the accuracy of Vp.

Cerebral toxoplasmosis in a patient with multiple myeloma.

Background: Cerebral toxoplasmosis is a rare complication of relapsed/refractory multiple myeloma (MM) after autologous stem cell transplant (SCT). Imaging characteristics can be helpful in leading to rapid diagnosis and treatment. Case Description: A 76-year-old man with relapsed/refractory IgA kappa MM status post autologous SCT who presented to the hospital with altered mental status. His hospital course was complicated by rapid decompensation to obtundation requiring intubation. Magnetic resonance imaging (MRI) of the brain revealed numerous ring-enhancing lesions with eccentric target signs, which were concerning for cerebral toxoplasmosis. Diagnosis was confirmed with positive toxoplasma cerebrospinal fluid polymerase chain reaction test. Conclusion: Cerebral toxoplasmosis should be considered in the differential diagnosis for MM patients who present with altered mental status and neurologic findings. The ring-enhancing lesion with eccentric target sign on MRI can be helpful in the diagnosis of cerebral toxoplasmosis.

MRI Findings of Arachnoiditis, Revisited. Is Classification Possible?

BACKGROUND: Prior imaging studies characterizing lumbar arachnoiditis have been based on small sample numbers and have reported inconsistent results. PURPOSE: To review the different imaging patterns of lumbosacral arachnoiditis, their significance, and clinical implications. STUDY TYPE: Retrospective. POPULATION: A total of 96 patients (43 women; average age 61.3 years) with imaging findings of arachnoiditis (postsurgical: N = 49; degenerative: N = 29; vertebral fracture: N = 6; epidural and subdural hemorrhage: N = 3, infectious: N= 1; other: N = 8) from January 2009 to April 2018. FIELD STRENGTH/SEQUENCE: Sagittal and axial T2-weighted Turbo Spin Echo at 1.5 T and 3 T. ASSESSMENT: Chart review was performed to assess the cause of arachnoiditis, and imaging was reviewed by two musculoskeletal and three neurology radiologists, blinded to the clinical data and to each other's imaging interpretation. Previous classification included a three-group system based on the appearance of the nerve roots on T2-weighted images. A fourth group was added in our review as "nonspecified" and was proposed for indeterminate imaging findings that did not fall into the classical groups. The presence/absence of synechiae/fibrous bands that distort the nerve roots and of spinal canal stenosis was also assessed. STATISTICAL TESTS: The kappa score was used to assess agreement between readers for both classification type and presence/absence of synechiae. RESULTS: Postsurgical (51%) and degenerative changes (30%) were the most common etiologies. About 7%-55% of arachnoiditis were classified as group 4. There was very poor classification agreement between readers (kappa score 0.051). There was also poor interreader agreement for determining the presence of synechiae (kappa 0.18) with, however, strong interreader agreement for the presence of synechia obtained between the most experienced readers (kappa 0.89). DATA CONCLUSION: This study demonstrated the lack of consensus and clarity in the classification system of lumbar arachnoiditis. The presence of synechia has high interreader agreement only among most experienced readers and promises to be a useful tool in assessing arachnoiditis. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

T1-weighted Dynamic Contrast-enhanced MRI to Differentiate Nonneoplastic and Malignant Vertebral Body Lesions in the Spine.

Background Dynamic contrast agent-enhanced (DCE) perfusion MRI may help differentiate between nonneoplastic and malignant lesions in the spine. Purpose To investigate the correlation between fractional plasma volume (Vp), a parameter derived from DCE perfusion MRI, and histopathologic diagnosis for spinal lesions. Materials and Methods In this retrospective study, patients who underwent DCE perfusion MRI and lesion biopsy between May 2015 and May 2018 were included. Inclusion criteria were short time interval (<30 days) between DCE perfusion MRI and biopsy, DCE perfusion MRI performed before biopsy, and DCE perfusion MRI performed at the same spine level as biopsy. Exclusion criteria were prior radiation treatment on vertebrae of interest, poor DCE perfusion MRI quality, nondiagnostic biopsy, and extensive spinal metastasis or prior kyphoplasty. One hundred thirty-four lesions were separated into a nonneoplastic group (n = 51) and a malignant group (n = 83) on the basis of histopathologic analysis. Two investigators manually defined regions of interest in the vertebrae. DCE perfusion MRI parameter Vp was calculated by using the Tofts pharmacokinetic two-compartment model. Vp was quantified, normalized to adjacent normal vertebrae, and compared between the two groups. A Mann-Whitney U test and receiver operating characteristic analysis was performed to verify the difference in Vp between the nonneoplastic and malignant groups. Reproducibility was assessed by calculating the Cohen κ coefficient. Results One hundred patients (mean age, 65 years ± 11 [standard deviation]; 52 men) were evaluated. Vp was lower in nonneoplastic lesions versus malignant lesions (1.6 ± 1.3 vs 4.2 ± 3.0, respectively; P < .001). The sensitivity of Vp was 93% (77 of 83; 95% confidence interval [CI]: 85%, 97%), specificity was 78% (40 of 51; 95% CI: 65%, 89%), and area under the receiver operating characteristic curve was 0.88 (95% CI: 0.82, 0.95). Cohen κ coefficient suggested substantial agreement in both intra- (κ = 0.72) and interreader (κ = 0.70) reproducibility. Conclusion This study indicated that dynamic contrast agent-enhanced perfusion MRI parameter, fractional plasma volume, was able to differentiate between nonneoplastic spinal lesions and malignant lesions. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Haller in this issue.

Long-Term Outcome After Conventional Two-Stage Hepatectomy Versus Tourniquet-ALPPS in Colorectal Liver Metastases: A Propensity Score Matching Analysis.

BACKGROUND: To compare the overall survival (OS) and disease-free survival (DFS) of Tourniquet-ALPPS (T-ALPPS) and conventional two-stage hepatectomy (TSH) in patients with colorectal liver metastases (CRLM). METHODS: A retrospective study from a prospectively collected database was performed between October 2000 and July 2016. TSH was performed before September 2011, after which time T-ALPPS became the technique of choice. A propensity score matching (PSM) was performed based on a 1:1 ratio with consideration of the following variables: number and size of metastases, bilobar disease presence, and chemotherapy received. RESULTS: Thirty-four patients received T-ALPPS; 41 patients received TSH. After PSM, 21 patients remained in each group, with 100% resectability in the T-ALPPS group and 90.5% resectability in the TSH group. The median OS for TSH was 41 months; for T-ALPPS, the median OS was 36 months (P = 0.925). The median DFS was 16 months in the TSH group; the median DFS was 9 months in the T-ALPPS group (P = 0.930). The 1-, 3-, and 5-year OS for TSH was 81%, 66.7%, and 23.8% vs. 76.2%, 57.1%, and 22.9% for T-ALPPS, respectively. The 1-, 3-, and 5-year DFS for TSH was 66.7%, 9.5%, and 5% vs. 44.6%, 11.1%, and 11.1% for T-ALPPS, respectively. The volume increase with T-ALPPS was superior to that with TSH (68% vs. 39%; P = 0.018). There were no differences in morbidity and mortality after stages 1 and 2. CONCLUSIONS: T-ALPPS produces a similar outcome to TSH, indicating that it could be a safe and effective alternative for curative hepatectomy for all patients.

ALPPS for hepatocarcinoma under cirrhosis: a feasible alternative to portal vein embolization.

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors. Preoperative portal vein embolization (PVE) is currently the most accepted treatment before major hepatic resection for HCC in patients with liver fibrosis or cirrhosis and associated insufficient future liver remnant (FLR). In the last decade, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has been described to obtain an increase of volume regarding PVE and a decrease of drop out. The initial excessive morbidity and mortality of this technique have decreased drastically due to a better selection of patients, the learning curve and the use of less aggressive variations of the original technique in the first stage. For both techniques a complete preoperative assessment of the FLR is the most important issue and only patients with and adequate FLR should be resected. ALPPS could be a feasible technique in very selected patients with HCC and cirrhosis. As long as it is performed in an experienced center could be used as a first choice technique versus PVE or could be used as a rescue technique in case of PVE failure.

Tourniquet-ALPPS is a promising treatment for very large hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

When very large hepatocellular carcinomas (HCCs) and intrahepatic cholangiocarcinoma (IHCCs) with insufficient future liver remnants are treated using associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), the outcome is often poor. We therefore tested the efficacy of a modified version of that technique, tourniquet-ALPPS. A review of the literature examining outcomes of HCC and IHCC patients treated with ALPPS revealed the incidences of morbidity ≥ III and postoperative mortality to be respectively 20.7% and 16.1% among HCC patients and 50% and 45.4% among IHCC patients. In the present case series, in which HCC and IHCC patients were treated with tourniquet-ALPPS, median tumor size was 100 mm (range: 70-200 mm). After surgical stage I, there was no morbidity, no mortality and the median future liver remnant had increased at day 7 by 76%. In surgical stage II, 100% of tumors were resectable (8 right trisectionectomies, 5 with inferior vena cava resection). Two patients experienced serious morbidity ≥ IIIB and 1 patient died (11%). One- and 3-year overall survival was 75% and 60%, respectively. Thus tourniquet-ALPPS appears to be an effective alternative to classical ALPPS for the treatment of patients with HCC or IHCC.

Reintervención tras complicaciones en cirugía laparoscópica colorrectal. ¿Aporta ventajas el abordaje laparoscópico? / Reoperation after laparoscopic colorectal surgery. Does the laparoscopic approach have any advantages?

Introducción: El abordaje laparoscópico en la cirugía por complicaciones colorrectales es controvertido. Sin embargo, puede proporcionar ventajas sobre la cirugía abierta. El objetivo del estudio es comparar el abordaje laparoscópico vs. el abordaje abierto en la reintervención por complicaciones tras cirugía colorrectal. Métodos: Se han analizado de forma retrospectiva, sobre una base de datos prospectiva, los pacientes intervenidos mediante cirugía laparoscópica colorrectal desde enero de 2006 a diciembre de 2015. Los pacientes que requirieron reintervenciones urgentes por complicaciones en el postoperatorio se dividieron según el abordaje (cirugía laparoscópica [CL] y cirugía abierta [CA]) y según su gravedad clínica (en función del índice de peritonitis de Mannheim [IPM]). Resultados: De 763 pacientes, 40 requirieron cirugía urgente (24 CA/16 CL). Se realizaron más ileostomías en el grupo CL (68,7% vs. 29,2%) y más colostomías en el grupo CA (37,5% vs. 6,2%), p<0,05. El IPM fue mayor en el grupo CA (27,31±6,47 [19-35] vs. 18,4±7,2 [11-24], p<0,001). La estancia hospitalaria tras la reintervención, tolerancia oral e infección de herida quirúrgica fueron favorables en CL (p<0,05). En pacientes con un IPM≤26, el abordaje laparoscópico mostró menor estancia hospitalaria, menor permanencia en unidad de críticos, tolerancia oral más temprana y menor infección de herida quirúrgica (p<0,05). Conclusiones: El abordaje laparoscópico en la reintervención por complicaciones tras cirugía colorrectal laparoscópica asocia una recuperación más rápida objetivada en un inicio precoz de tolerancia oral, menor estancia hospitalaria y menor tasa de hernia incisional en pacientes con bajo índice de gravedad (AU)

Introduction: The laparoscopic approach in colorectal complications is controversial because of its difficulty. However, it has been proven that it can provide advantages over open surgery. The aim of this study is to compare laparoscopic approach in reoperations for complications after colorectal surgery with the open approach taking into account the severity of the patient prior to reoperation. Methods: Patients who underwent laparoscopic colorectal surgery from January 2006 to December 2015 were retrospectively reviewed. Patients requiring urgent surgical procedures for complications in the postoperative period were divided in two groups: laparoscopic surgery (LS) and open surgery (OS). To control clinical severity prior to reoperation, The Mannheim Peritonitis Index (MPI) was calculated. Results: A total of 763 patients were studied, 40 required urgent surgery (24 OS/16 LS). More ileostomies were performed in the LS group (68.7% vs. 29.2%) and more colostomies in the OS group (37.5% vs. 6.2%), p<0.05. MPI was higher in OS group (27.31±6.47 [19-35] vs. 18.36±7.16 [11-24], p<0.001). Hospital stay after re-intervention, oral tolerance and surgical wound infection, were favorable in LS (p<0.05 in all cases). In patients with MPI score ≤26, laparoscopic approach showed shorter hospital stay after re-intervention, less stay in the critical care unit after re-intervention, earlier start of oral tolerance and less surgical wound infection (p<0.05). Conclusions: A laparoscopic approach in re-intervention for complications after laparoscopic colorectal surgery associates a faster recovery reflected in a shorter hospital stay, earlier start of oral tolerance and a lower abdominal wall complication rate in patients with low severity index (AU)

Reoperation after laparoscopic colorectal surgery. Does the laparoscopic approach have any advantages? / Reintervención tras complicaciones en cirugía laparoscópica colorrectal. ¿Aporta ventajas el abordaje laparoscópico?

INTRODUCTION: The laparoscopic approach in colorectal complications is controversial because of its difficulty. However, it has been proven that it can provide advantages over open surgery. The aim of this study is to compare laparoscopic approach in reoperations for complications after colorectal surgery with the open approach taking into account the severity of the patient prior to reoperation. METHODS: Patients who underwent laparoscopic colorectal surgery from January 2006 to December 2015 were retrospectively reviewed. Patients requiring urgent surgical procedures for complications in the postoperative period were divided in two groups: laparoscopic surgery (LS) and open surgery (OS). To control clinical severity prior to reoperation, The Mannheim Peritonitis Index (MPI) was calculated. RESULTS: A total of 763 patients were studied, 40 required urgent surgery (24 OS/16 LS). More ileostomies were performed in the LS group (68.7% vs. 29.2%) and more colostomies in the OS group (37.5% vs. 6.2%), p<0.05. MPI was higher in OS group (27.31±6.47 [19-35] vs. 18.36±7.16 [11-24], p<0.001). Hospital stay after re-intervention, oral tolerance and surgical wound infection, were favorable in LS (p<0.05 in all cases). In patients with MPI score ≤26, laparoscopic approach showed shorter hospital stay after re-intervention, less stay in the critical care unit after re-intervention, earlier start of oral tolerance and less surgical wound infection (p<0.05). CONCLUSIONS: A laparoscopic approach in re-intervention for complications after laparoscopic colorectal surgery associates a faster recovery reflected in a shorter hospital stay, earlier start of oral tolerance and a lower abdominal wall complication rate in patients with low severity index.

Calcifying pseudoneoplasm of the spine: imaging and pathological features.

Calcifying pseudoneoplasms of the neuraxis are extremely rare calcified lesions that can occur anywhere in the central nervous system. These non-neoplastic lesions have been reported to arise both in the brain and spine with similar frequency and can be found intra-axially as well as extra-axially. The associated symptoms are generally due to mass effect rather than local invasion as calcifying pseudoneoplasms of the neuraxis are usually considered to be benign non-infiltrative lesions. We report a unique case of a 67-year-old male patient who developed lower extremity weakness and gait instability with imaging and histological features of calcifying pseudoneoplasm of the neuraxis occurring in the spine with adhesive features and intradural extension. Calcifying pseudoneoplasms are benign, slow-growing masses that can present with a wide variety of symptoms depending on the size and location of the tumor. The differential diagnosis for these entities can be narrowed taking into consideration relevant imaging features as well as important clinical information.

Diffusion Tensor Imaging Shows Corpus Callosum Differences between High-Grade Gliomas and Metastases.

BACKGROUND AND PURPOSE: The corpus callosum (CC) has an important role in regulating interhemispheric transfer and is thought to be instrumental in contralateral brain reorganization in patients with brain tumors, as suggested by a previous study reporting callosal differences between language dominance groups through diffusion tensor imaging (DTI) characteristics. The purpose of this study was to explore the structural differences in the CC between high-grade gliomas (HGGs) and metastatic tumors (METs) using the DTI characteristics of fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD). METHODS: HGG (n = 30) and MET (n = 20) subjects with Magnetic Resonance Imaging (MRI) scans including DTI were retrospectively studied. The tumor and CC were segmented using the 3-dimensional T1-weighted scans to determine their volumes. The region of interest (ROI; mean volume of the ROI = 3,090 ± 464 mm3 ) of the body of the CC was overlaid onto the DTI parametric maps to obtain the averaged FA, MD, and AD values. RESULTS: There were significant differences in the distributions of FA and MD values between the two patient groups (mean FA for HGG/MET = .691/.646, P < .05; mean MD for HGG/MET = .894×10-3 mm 2/ second /.992×10-3 mm2 /second, P < .01), while there was no correlation between the DTI parameters and the anatomical volumes. CONCLUSION: These results suggest that there is more contralateral brain reorganization in HGG patients than MET patients and that neither the tumor nor callosal volume impact the degree of contralateral brain reorganization.

Stereotactic body radiotherapy for metastatic spinal sarcoma: a detailed patterns-of-failure study.

OBJECTIVE The aim of this study was to report the first detailed analysis of patterns of failure within the spinal axis of patients treated with stereotactic body radiotherapy (SBRT) for sarcoma spine metastases. METHODS Between 2005 and 2012, 88 consecutive patients with metastatic sarcoma were treated with SBRT for 120 spinal lesions. Seventy-one percent of patients were enrolled on prospective institutional protocols. For patients who underwent routine posttreatment total-spine MRI (64 patients, 88 lesions), each site of progression within the entire spinal axis was mapped in relation to the treated lesion. Actuarial rates of local-, adjacent-, and distant-segment failure-free survival (FFS) were calculated using the Kaplan-Meier method. RESULTS The median follow-up for the cohort was 14.4 months, with 81.7% of patients followed up until death. The 12-month actuarial rate of local FFS was 85.9%; however, 83.3% of local failures occurred in conjunction with distant-segment failures. The 12-month actuarial rates of isolated local-, adjacent-, and distant-segment FFS were 98.0%, 97.8%, and 74.7%, respectively. Of patients with any spinal progression (n = 55), only 25.5% (n = 14) had progression at a single vertebral level, with 60.0% (n = 33) having progression at ≥ 3 sites within the spine simultaneously. Linear regression analysis revealed a relationship of decreasing risk of failure with increasing distance from the treated index lesion (R(2) = 0.87), and 54.1% of failures occurred ≥ 5 vertebral levels away. Treatment of the index lesion with a lower biological effective dose (OR 3.2, 95% CI 1.1-9.2) and presence of local failure (OR 18.0, 95% CI 2.1-152.9) independently predicted for distant spine failure. CONCLUSIONS Isolated local- and adjacent-segment failures are exceptionally rare for patients with metastatic sarcoma to the spine treated with SBRT, thereby affirming the treatment of the involved level only. The majority of progression within the spinal axis occurs ≥ 5 vertebral levels away. Thus, total-spine imaging is necessary for surveillance posttreatment.

Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients.

BACKGROUND: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS. METHODS: We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05. RESULTS: Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004). CONCLUSIONS: The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.

Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases.

BACKGROUND CONTEXT: Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. PURPOSE: This study aimed to identify early magnetic resonance imaging (MRI) biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. STUDY DESIGN/SETTING: This study used a retrospective case series at a large tertiary cancer center. PATIENT SAMPLE: From 2011 to 2014, 9 consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) both pre- and post-SBRT. OUTCOME MEASURE: Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multiparametric magnetic resonance imaging (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. METHODS: All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t tests were used to compare groups. p<.05 was deemed statistically significant. RESULTS: The median time from SBRT until posttreatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. The Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared with pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of "worsening," "no change," or "improvement," respectively, by both radiologists' graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2=0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared with the mpMRI score change post-SBRT (R2=0.026). CONCLUSIONS: We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at 2 months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.

Corpus Callosum Diffusion and Language Lateralization in Patients with Brain Tumors: A DTI and fMRI Study.

BACKGROUND AND PURPOSE: Examining how left-hemisphere brain tumors might impact both the microstructure of the corpus callosum (CC) as measured by fractional anisotropy (FA) values in diffusion tensor imaging (DTI) as well as cortical language lateralization measured with functional MRI (fMRI). METHODS: fMRI tasks (phonemic fluency and verb generation) were performed in order to detect activation in Broca's and Wernicke's area. Twenty patients with left-hemisphere brain tumors were investigated. fMRI results were divided into left dominant (LD), right dominant (RD), or codominant (CD) for language function. DTI was performed to generate FA maps in the anterior and posterior CC. FA values were correlated with the degree of language dominance. RESULTS: Patients who were LD or RD for language in Broca's area had lower FA in the anterior CC than those who were CD for language (median for CD = .72, LD = .66, RD = .65, P < .09). Lateralized versus CD group level analysis also showed that CD patients had higher FA in the anterior CC than patients who displayed strong lateralization in either hemisphere (median for CD = .72, lateralized = .65, P < .05). CONCLUSION: Our preliminary observations indicate that the greater FA in CD patients may reflect a more directional microstructure for the CC in this region, suggesting a greater need for interhemispheric transfer of information. Because brain tumors can cause compensatory codominance, our findings may suggest a mechanism by which interhemispheric transfer is facilitated during plasticity in the presence of a tumor.