Subdural hematoma prevalence and long-term developmental outcomes in patients with benign expansion of the subarachnoid spaces.

OBJECTIVE: Benign expansion of the subarachnoid spaces (BESS) is a condition seen in macrocephalic infants. BESS is associated with mild developmental delays which tend to resolve within a few years. It is accepted that patients with BESS are at increased risk of spontaneous subdural hematomas (SDHs), although the exact pathophysiology is not well understood. The prevalence of spontaneous SDH in BESS patients is poorly defined, with only a few large single-center series published. In this study the authors aimed to better define BESS prevalence and developmental outcomes through the longitudinal review of a large cohort of BESS patients. METHODS: A large retrospective review was performed at a single institution from 1995 to 2020 for patients 2 years of age or younger with a diagnosis of BESS by neurology or neurosurgery and head circumference > 85th percentile. Demographic data, head circumference, presence of developmental delay, occurrence of SDH, and need for surgery were extracted from patient charts. The subarachnoid space (SAS) size was measured from the available MR images, and the sizes of those who did and did not develop SDH were compared. RESULTS: Free text search revealed BESS mentioned within the medical records of 1410 of 2.6 million patients. After exclusion criteria, 480 patients remained eligible for the study. Thirty-two percent (n = 154) of patients were diagnosed with developmental delay, most commonly gross motor delay (53%). Gross motor delay resolved in 86% of patients at a mean age of 22.2 months. The prevalence of spontaneous SDH in this BESS population over a period of 25 years was 8.1%. There was no significant association between SAS size and SDH formation. CONCLUSIONS: This study represents results for one of the largest cohorts of patients with BESS at a single institution. Gross motor delay was the most common developmental delay diagnosed, and a majority of patients had resolution of their delay. These data support that children with BESS have a higher prevalence of SDH than the general pediatric population, although SAS size was not significantly associated with SDH development.

Survival Prediction Analysis in Glioblastoma With Diffusion Kurtosis Imaging.

SIMPLE SUMMARY: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Diffusion kurtosis imaging (DKI) has characterized non-Gaussian diffusion behaviors in brain normal tissue and gliomas, but there are very limited efforts in investigating treatment responses of kurtosis in GBM. This study aimed to investigate whether any parameter derived from the DKI is a significant predictor of overall survival (OS). We found that the large mean, 80 and 90 percentile kurtosis values in the contrast enhanced gross tumor volume (Gd-GTV) on post-Gd T1-weighted images pre-RT were significantly associated with reduced OS. In the multivariate Cox model, the mean kurtosis Gd-GTV pre-RT after considering effects of age, extent of surgery, and methylation were significant predictors of OS. In addition, the 80 and 90 percentile kurtosis values in Gd-GTV post RT were significantly associated with progression free survival (PFS). The DKI model demonstrates the potential to predict outcomes in the patients with GBM. PURPOSE: Non-Gaussian diffusion behaviors in gliomas have been characterized by diffusion kurtosis imaging (DKI). But there are very limited efforts in investigating the kurtosis in glioblastoma (GBM) and its prognostic and predictive values. This study aimed to investigate whether any of the diffusion kurtosis parameters derived from DKI is a significant predictor of overall survival. METHODS AND MATERIALS: Thirty-three patients with GBM had pre-radiation therapy (RT) and mid-RT diffusion weighted (DW) images. Kurtosis and diffusion coefficient (DC) values in the contrast enhanced gross tumor volume (Gd-GTV) on post-Gd T1 weighted images pre-RT and mid-RT were calculated. Univariate and multivariate Cox models were used to evaluate the DKI parameters and clinical factors for prediction of OS and PFS. RESULTS: The large mean kurtosis values in the Gd-GTV pre-RT were significantly associated with reduced OS (p = 0.02), but the values at mid-RT were not (p > 0.8). In the multivariate Cox model, the mean kurtosis in the Gd-GTV pre-RT (p = 0.009) was still a significant predictor of OS after adjusting effects of age, O6-Methylguanine-DNA Methyl transferase (MGMT) methylation and extent of resection. In Gd-GTV post-RT, 80 and 90 percentile kurtosis values were significant predictors (p ≤ 0.05) for progression free survival (PFS). CONCLUSION: The DKI model demonstrates the potential to predict OS and PFS in the patients with GBM. Further development and histopathological validation of the DKI model will warrant its role in clinical management of GBM.

Safety and diagnostic efficacy of gadoteridol for magnetic resonance imaging of the brain and spine in children 2 years of age and younger.

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers. RESULTS: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively). CONCLUSION: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age.

Imaging Errors in Distinguishing Pituitary Adenomas From Other Sellar Lesions.

BACKGROUND: Pituitary adenomas and nonadenomatous lesions in the sellar region may be difficult to distinguish by imaging yet that distinction is critical in guiding management. The nature of the diagnostic errors in this setting has not been well documented. METHODS: Two neurosurgeons and 2 neuroradiologists of differing experience levels viewed deidentified MRIs of 18 nonadenomatous sellar lesions and 21 adenomas. They recorded their diagnoses, the imaging features they used to make those diagnoses, and their confidence in making those diagnoses. RESULTS: Among the 18 nonadenoma cases, 11 (61%) were incorrectly diagnosed as adenoma by at least 1 reader, including Rathke cleft cyst, plasmacytoma, aneurysm, craniopharyngioma, chordoma, Langerhans cell histiocytosis, metastasis, and undifferentiated sinonasal carcinoma. Among the 21 adenoma cases, 8 (38%) were incorrectly diagnosed by at least 1 reader as craniopharyngioma, Rathke cleft cyst, sinonasal carcinoma, hemangioblastoma, and pituitary hyperplasia. Incorrect imaging diagnoses were made with high confidence in 13% of readings. Avoidable errors among the nonadenomatous cases occurred when readers failed to appreciate that the lesion was separate from the pituitary gland. Unavoidable errors in those cases occurred when the lesions were so large that the pituitary gland had been obliterated or the imaging features of a nonadenomatous lesion resembled those of a cystic pituitary adenoma. Avoidable errors in misdiagnosis of adenomas as nonadenomas occurred when readers failed to appreciate features highly characteristic of adenomas. An unavoidable error occurred because a cystic adenoma had features correctly associated with craniopharyngioma. CONCLUSIONS: Errors in imaging differentiation of pituitary adenoma from nonadenomatous lesions occurred often and sometimes with high confidence among a small sample of neurosurgeons and neuroradiologists. In the misdiagnosis of nonadenomatous lesions as adenomas, errors occurred largely from failure to appreciate a separate pituitary gland, but unavoidable errors occurred when large lesions had obliterated this distinguishing feature. In the misdiagnosis of adenomas as nonadenomatous lesions, avoidable errors occurred because readers failed to recognize imaging features more characteristic of adenomas and because cystic adenomas share features with craniopharyngiomas and Rathke cleft cysts. Awareness of these errors should lead to improved management of sellar lesions.

Response assessment during chemoradiation using a hypercellular/hyperperfused imaging phenotype predicts survival in patients with newly diagnosed glioblastoma.

BACKGROUND: Adversely prognostic hypercellular and hyperperfused regions of glioblastoma (GBM) predict progression-free survival, and are a novel target for dose-intensified chemoradiation (chemoRT) recently implemented in a phase II clinical trial. As a secondary aim, we hypothesized that dose-intensified chemoRT would induce greater mid-treatment response of hypercellular/hyperperfused tumor regions vs standard chemoradiation, and that early response would improve overall survival (OS). METHODS: Forty-nine patients with newly diagnosed GBM underwent prospective, multiparametric high b value diffusion-weighted MRI (DW-MRI) and perfusion dynamic contrast-enhanced MRI (DCE-MRI) pre-RT and 3-4 weeks into RT. The hypercellular tumor volume (TVHCV, mean contralateral normal brain + 2SD) and hyperperfused tumor volume (TVCBV, contralateral normal frontal gray matter + 1SD) were generated using automated thresholding. Twenty-six patients were enrolled on a dose-escalation trial targeting TVHCV/TVCBV with 75 Gy in 30 fractions, and 23 non-trial patients comprised the control group. OS was estimated using the Kaplan-Meier method and compared using the log-rank test. The effect of TVHCV/TVCBV and Gd-enhanced tumor volume on OS was assessed using multivariable Cox proportional-hazard regression. RESULTS: Most patients had gross total (47%) or subtotal resection (37%), 25% were MGMT-methylated. Patients treated on the dose-escalation trial had significantly greater reduction in TVHCV/TVCBV (41% reduction, IQR 17%-75%) vs non-trial patients (6% reduction, IQR 6%-22%, P = .002). An increase in TVHCV/TVCBV during chemoRT was associated with worse OS (adjusted hazard ratio [aHR] 1.2, 95%CI 1.0-1.4, P = .02), while pre-treatment tumor volumes (P > .5) and changes in Gd-enhanced volume (P = .9) were not. CONCLUSIONS: Multiparametric MRI permits identification of therapeutic resistance during chemoRT and supports adaptive strategies in future trials.

A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma.

PURPOSE: We hypothesized that dose-intensified chemoradiation therapy targeting adversely prognostic hypercellular (TVHCV) and hyperperfused (TVCBV) tumor volumes would improve outcomes in patients with glioblastoma. METHODS AND MATERIALS: This single-arm, phase 2 trial enrolled adult patients with newly diagnosed glioblastoma. Patients with a TVHCV/TVCBV >1 cm3, identified using high b-value diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced perfusion MRI, were treated over 30 fractions to 75 Gy to the TVHCV/TVCBV with temozolomide. The primary objective was to estimate improvement in 12-month overall survival (OS) versus historical control. Secondary objectives included evaluating the effect of 3-month TVHCV/TVCBV reduction on OS using Cox proportional-hazard regression and characterizing coverage (95% isodose line) of metabolic tumor volumes identified using correlative 11C-methionine positron emission tomography. Clinically meaningful change was assessed for quality of life by the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30, for symptom burden by the MD Anderson Symptom Inventory for brain tumor, and for neurocognitive function (NCF) by the Controlled Oral Word Association Test, the Trail Making Test, parts A and B, and the Hopkins Verbal Learning Test-Revised. RESULTS: Between 2016 and 2018, 26 patients were enrolled. Initial patients were boosted to TVHCV alone, and 13 patients were boosted to both TVHCV/TVCBV. Gross or subtotal resection was performed in 87% of patients; 22% were O6-methylguanine-DNA methyltransferase (MGMT) methylated. With 26-month follow-up (95% CI, 19-not reached), the 12-month OS rate among patients boosted to the combined TVHCV/TVCBV was 92% (95% CI, 78%-100%; P = .03) and the median OS was 20 months (95% CI, 18-not reached); the median OS for the whole study cohort was 20 months (95% CI, 14-29 months). Patients whose 3-month TVHCV/TVCBV decreased to less than the median volume (3 cm3) had superior OS (29 vs 12 months; P = .02). Only 5 patients had central or in-field failures, and 93% (interquartile range, 59%-100%) of the 11C-methionine metabolic tumor volumes received high-dose coverage. Late grade 3 neurologic toxicity occurred in 2 patients. Among non-progressing patients, 1-month and 7-month deterioration in quality of life, symptoms, and NCF were similar in incidence to standard therapy. CONCLUSIONS: Dose intensification against hypercellular/hyperperfused tumor regions in glioblastoma yields promising OS with favorable outcomes for NCF, symptom burden, and quality of life, particularly among patients with greater tumor reduction 3 months after radiation therapy.

Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma.

Pediatric and adult high-grade gliomas (HGGs) frequently harbor PDGFRA alterations. We hypothesized that cotreatment with everolimus may improve the efficacy of dasatinib in PDGFRα-driven glioma through combinatorial synergism and increased tumor accumulation of dasatinib. We performed dose-response, synergism, P-glycoprotein inhibition, and pharmacokinetic studies in in vitro and in vivo human and mouse models of HGG. Six patients with recurrent PDGFRα-driven glioma were treated with dasatinib and everolimus. We found that dasatinib effectively inhibited the proliferation of mouse and human primary HGG cells with a variety of PDGFRA alterations. Dasatinib exhibited synergy with everolimus in the treatment of HGG cells at low nanomolar concentrations of both agents, with a reduction in mTOR signaling that persisted after dasatinib treatment alone. Prolonged exposure to everolimus significantly improved the CNS retention of dasatinib and extended the survival of PPK tumor-bearing mice (mutant TP53, mutant PDGFRA, H3K27M). Six pediatric patients with glioma tolerated this combination without significant adverse events, and 4 patients with recurrent disease (n = 4) had a median overall survival of 8.5 months. Our results show that the efficacy of dasatinib treatment of PDGFRα-driven HGG was enhanced with everolimus and suggest a promising route for improving targeted therapy for this patient population.

Microstructure Modeling of High b-Value Diffusion-Weighted Images in Glioblastoma.

Apparent diffusion coefficient has limits to differentiate solid tumor from normal tissue or edema in glioblastoma (GBM). This study investigated a microstructure model (MSM) in GBM using a clinically available diffusion imaging technique. The MSM was modified to integrate with bi-polar diffusion gradient waveforms, and applied to 30 patients with newly diagnosed GBM. Diffusion-weighted (DW) images acquired on a 3 T scanner with b-values from 0 to 2500 s/mm2 were fitted in volumes of interest (VOIs) of solid tumor to obtain the apparent restriction size of intracellular water (ARS), the fractional volume of intracellular water (Vin ), and extracellular (Dex ) water diffusivity. The parameters in solid tumor were compared with those of other tissue types by Students' t test. For comparison, DW images were fitted by conventional mono-exponential and bi-exponential models. ARS, Dex , and Vin from the MSM in tumor VOIs were significantly greater than those in WM, GM, and edema (P values of .01-.001). ARS values in solid tumors (from 21.6 to 34.5 um) had absolutely no overlap with those in all other tissue types (from 0.9 to 3.5 um). Vin values showed a descending order from solid tumor (from 0.32 to 0.52) to WM, GM, and edema (from 0.05 to 0.25), consisting with the descending cellularity in these tissue types. The parameters from mono-exponential and bi-exponential models could not significantly differentiate solid tumor from all other tissue types, particularly from edema. Further development and histopathological validation of the MSM will warrant its role in clinical management of GBM.

BRAINSTORM: A Multi-Institutional Phase 1/2 Study of RRx-001 in Combination With Whole Brain Radiation Therapy for Patients With Brain Metastases.

PURPOSE: To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response. METHODS AND MATERIALS: Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose escalation was managed by the time-to-event continual reassessment method algorithm. Linear mixed models were used to correlate change in 24-hour T1, Ktrans (capillary permeability), and fractional plasma volume with change in tumor volume. RESULTS: Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The most common tumor types were melanoma (59%) and non-small cell lung cancer (18%). No dose limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia (6.9%, 2 of 29). The median intracranial response rate was 46% (95% confidence interval, 24-68) and median overall survival was 5.2 months (95% confidence interval, 4.5-9.4). No neurologic deaths occurred. Among 10 patients undergoing dynamic contrast-enhanced MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 and 4 months (P ≤ .01). CONCLUSIONS: The addition of RRx-001 to WBRT is well tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, the recommended phase 2 dose is 10 mg twice weekly. A reduction in fractional plasma volume on dynamic contrast-enhanced MRI 24 hours after RRx-001 suggests antiangiogenic activity associated with longer-term tumor response.

Catastrophic Allergic Fungal Sinusitis: A Report of Two Cases.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a common condition in which sinusitis develops as an IgE-mediated response to common sinonasal fungal organisms. If that response leads to blockage of sinus ostia, bone expansion and erosion by expansive cysts containing dense inspissated debris may occur with the potential for critical neurovascular compression including damage to the anterior visual pathway. METHODS: Review of clinical and imaging features of 2 patients who sustained catastrophic clinical outcomes. RESULTS: The first patient had pansinusitis with massive mucocele-like cysts expanding the sphenoid sinus and cranial base and causing compression of the anterior visual pathway that led to persistent severe vision loss despite extensive sinus surgery. The second patient developed sphenoethmoidal expansion with a marked inflammatory response and presumed conversion to invasive fungal sinusitis that caused anterior visual pathway vision loss, bilateral ocular motor palsies from extension into the cavernous sinuses, and death from a large middle cerebral artery stroke. CONCLUSIONS: Although AFRS is most often benign and treatable, it may rarely produce catastrophic outcomes, especially if the sphenoid sinus is involved. Irreversible vision loss may occur from compression, and ocular motor palsies and death from conversion to invasive fungal disease. Close ophthalmologic and imaging monitoring is necessary in patients with expanded sinuses, and prophylactic sinus surgery may be indicated in certain cases.

Neuroimaging features of CNS histiocytosis syndromes.

Histiocytosis syndromes (HS) are group of heterogeneous disorders characterized by abnormal accumulation and infiltration of histiocytes, cells derived from hematopoietic cells of monocyte/macrophage lineage. Overall these disorders are rare. When they do occur they involve many organ systems including the central nervous system (CNS). While imaging findings can provide important clues, diagnosis of this disorder is challenging and definitive diagnosis often necessitates pathologic examination. In this review, we describe imaging features of HS involving the CNS, with the aim to increase our understanding of these disorders. The entities discussed in this review will include: Langerhans cell histiocytosis (LCH), Rosai-Dorfman Disease (RDD), Erdheim Chester Disease (ECD), hemophagocytic lymphohistiocytosis (HLH), and crystal-storing histiocytosis (CSH).

Developing a Pipeline for Multiparametric MRI-Guided Radiation Therapy: Initial Results from a Phase II Clinical Trial in Newly Diagnosed Glioblastoma.

Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.

Combining Perfusion and High B-value Diffusion MRI to Inform Prognosis and Predict Failure Patterns in Glioblastoma.

PURPOSE: Advanced imaging modalities such as high b-value diffusion and dynamic contrast enhancement magnetic resonance imaging have the potential to improve the clinical management of glioblastoma by informing prognosis, predicting sites of progression, and guiding dose-escalated radiation to maximize tumor control and minimize toxicity. METHODS AND MATERIALS: Fifty-two patients with de novo glioblastoma underwent magnetic resonance imaging before chemoradiation therapy. Enhanced tumor volumes (TVs), excluding the surgical cavity, hypercellularity (TVHCV) and increased cerebral blood volume (TVCBV) were defined using conventional gadolinium-enhanced T1-weighted images, high b-value (3000 s/mm2) diffusion-weighted images, and cerebral blood volume maps from T1-weighted dynamic contrast enhancement images, respectively. The image-phenotype TVs were analyzed for prediction of progression-free survival (Cox proportional hazard models), and sites of progression (pattern of failure tumor volume). RESULTS: The median progression-free survival (PFS) of the cohort was 13 months. The TVCBV and TVHCV were spatially distinct, with a mean overlap of only 21%. Univariate analysis showed that increasing age, decreasing radiation dose, larger TVHCV, and larger overlap of TVHCV and TVCBV were significantly associated with inferior PFS. Multivariate analysis identified that TVHCV was the most adversely prognostic imaging-defined variable. Enhanced TVs, excluding the surgical cavity, and the union of TVHCV and TVCBV showed a high likelihood of containing the pattern of failure tumor volume, and the volume composed of the intersection of TVHCV and TVCBV had an especially high likelihood of progression. CONCLUSIONS: TVHCV and the overlap of TVHCV and TVCBV are prognostic for PFS. Combinations of gadolinium-enhanced TVs, TVCBV, and TVHCV could predict tumor progression locations better than could individual subvolumes. Radiation dose escalation to these subvolumes could be a promising therapeutic strategy.

Effects of an artificial placenta on brain development and injury in premature lambs.

PURPOSE: We evaluated whether brain development continues and brain injury is prevented during Artificial Placenta (AP) support utilizing extracorporeal life support (ECLS). METHODS: Lambs at EGA 118days (term=145; n=4) were placed on AP support (venovenous ECLS with jugular drainage and umbilical vein reinfusion) for 7days and sacrificed. Early (EGA 118; n=4) and late (EGA 127; n=4) mechanical ventilation (MV) lambs underwent conventional MV for up to 48h and were sacrificed, and early (n=5) and late (n=5) tissue control (TC) lambs were sacrificed at delivery. Brains were harvested, formalin-fixed, rehydrated, and studied by magnetic resonance imaging (MRI). The gyrification index (GI), a measure of cerebral folding complexity, was calculated for each brain. Diffusion-weighted imaging was used to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in multiple structures to assess white matter (WM) integrity. RESULTS: No intracranial hemorrhage was observed. GI was similar between AP and TC groups. ADC and FA did not differ between AP and late TC groups in any structure. Compared to late MV brains, AP brains demonstrated significantly higher ADC (0.45±0.08 vs. 0.27±0.11, p=0.02) and FA (0.61±0.04 vs. 0.44±0.05; p=0.006) in the cerebral peduncles. CONCLUSIONS: After 7days of AP support, WM integrity is preserved relative to mechanical ventilation. TYPE OF STUDY: Research study.

Tumor image signatures and habitats: a processing pipeline of multimodality metabolic and physiological images.

To create tumor "habitats" from the "signatures" discovered from multimodality metabolic and physiological images, we developed a framework of a processing pipeline. The processing pipeline consists of six major steps: (1) creating superpixels as a spatial unit in a tumor volume; (2) forming a data matrix [Formula: see text] containing all multimodality image parameters at superpixels; (3) forming and clustering a covariance or correlation matrix [Formula: see text] of the image parameters to discover major image "signatures;" (4) clustering the superpixels and organizing the parameter order of the [Formula: see text] matrix according to the one found in step 3; (5) creating "habitats" in the image space from the superpixels associated with the "signatures;" and (6) pooling and clustering a matrix consisting of correlation coefficients of each pair of image parameters from all patients to discover subgroup patterns of the tumors. The pipeline was applied to a dataset of multimodality images in glioblastoma (GBM) first, which consisted of 10 image parameters. Three major image "signatures" were identified. The three major "habitats" plus their overlaps were created. To test generalizability of the processing pipeline, a second image dataset from GBM, acquired on the scanners different from the first one, was processed. Also, to demonstrate the clinical association of image-defined "signatures" and "habitats," the patterns of recurrence of the patients were analyzed together with image parameters acquired prechemoradiation therapy. An association of the recurrence patterns with image-defined "signatures" and "habitats" was revealed. These image-defined "signatures" and "habitats" can be used to guide stereotactic tissue biopsy for genetic and mutation status analysis and to analyze for prediction of treatment outcomes, e.g., patterns of failure.

Reassessing the Anatomic Origin of the Juvenile Nasopharyngeal Angiofibroma.

OBJECTIVE: A modern imaging review is necessary to further define the anatomic origin of the juvenile nasopharyngeal angiofibroma. METHODS: After institutional review board approval, a search from January 1998 to January 2013 yielded 33 male patients (aged 10-23 years) with pathologically proven juvenile nasopharyngeal angiofibroma lesions, as well as pretreatment computed tomography/magnetic resonance imaging. Juvenile nasopharyngeal angiofibroma involvement was assessed in the following regions: sphenopalatine foramen, pterygopalatine fossa, vidian canal, nasopharynx, nasal cavity, sphenoid sinus, choana, pterygomaxillary fissure/masticator space, orbit, and sphenoid bone. RESULTS: The choana and nasopharynx were involved in all 33 patients. In contrast, only 22 lesions involved the pterygopalatine fossa, 24 lesions involved the sphenopalatine foramen, and 28 lesions involved the vidian canal. CONCLUSIONS: Our results suggest that the juvenile nasopharyngeal angiofibroma origin is in the region of the choana and nasopharynx rather than the sphenopalatine foramen or pterygopalatine fossa.

MR-guided radiation therapy: transformative technology and its role in the central nervous system.

This review article describes advancement of magnetic resonance imaging technologies in radiation therapy planning, guidance, and adaptation of brain tumors. The potential for MR-guided radiation therapy to improve outcomes and the challenges in its adoption are discussed.

Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

BACKGROUND: Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. SIGNIFICANCE: Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial.