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The highly aggressive nature of glioblastoma carries a dismal prognosis despite aggressive multimodal therapy. Alternative treatment regimens, such as immunotherapies, are known to intensify the inflammatory response in the treatment field. Follow-up imaging in these scenarios often mimics disease progression on conventional MRI, making accurate evaluation extremely challenging. To this end, revised criteria for assessment of treatment response in high-grade gliomas were successfully proposed by the RANO Working Group to distinguish pseudoprogression from true progression, with intrinsic constraints related to the postcontrast T1-weighted MRI sequence. To address these existing limitations, our group proposes a more objective and quantifiable “treatment agnostic” model, integrating into the RANO criteria advanced multimodal neuroimaging techniques, such as diffusion tensor imaging (DTI), dynamic susceptibility contrast-perfusion weighted imaging (DSC-PWI), dynamic contrast enhanced (DCE)-MRI, MR spectroscopy, and amino acid-based positron emission tomography (PET) imaging tracers, along with artificial intelligence (AI) tools (radiomics, radiogenomics, and radiopathomics) and molecular information to address this complex issue of treatment-related changes versus tumor progression in “real-time”, particularly in the early posttreatment window. Our perspective delineates the potential of incorporating multimodal neuroimaging techniques to improve consistency and automation for the assessment of early treatment response in neuro-oncology.

Purpose Autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) is a promising treatment modality for glioblastomas. The purpose of this study was to investigate the potential utility of multiparametric MRI-based prediction model in evaluating treatment response in glioblastoma patients treated with DCVax-L. Methods Seventeen glioblastoma patients treated with standard-of-care therapy + DCVax-L were included. When tumor progression was suspected and repeat surgery was being contemplated, we sought to ascertain the number of cases correctly classified as true progression (TP) + mixed response or pseudoprogression (PsP) from multiparametric MRI-based prediction model using histopathology/mRANO criteria as ground truth. Multiparametric MRI model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI-derived parameters. A comparison of overall survival (OS) was performed between patients treated with standard-of-care therapy + DCVax-L and standard-of-care therapy alone (external controls). Additionally, Kaplan-Meier analyses were performed to compare OS between two groups of patients using PsP, Ki-67, and MGMT methylation status as stratification variables. Results Multiparametric MRI model correctly predicted TP + mixed response in 72.7% of cases (8/11) and PsP in 83.3% (5/6) with an overall concordance rate of 76.5% with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.54; p = 0.026). DCVax-L-treated patients had significantly prolonged OS than those treated with standard-of-care therapy (22.38 ± 12.8 vs. 13.8 ± 9.5months, p = 0.040). Additionally, glioblastomas with PsP, MGMT methylation status, and Ki-67 values below median had longer OS than their counterparts. Conclusion Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

Objectives: To investigate the prognostic utility of DTI and DSC-PWI perfusion-derived parameters in brain metastases patients. Methods: Retrospective analyses of DTI-derived parameters (MD, FA, CL, CP, and CS) and DSC-perfusion PWI-derived rCBVmax from 101 patients diagnosed with brain metastases prior to treatment were performed. Using semi-automated segmentation, DTI metrics and rCBVmax were quantified from enhancing areas of the dominant metastatic lesion. For each metric, patients were classified as short- and long-term survivors based on analysis of the best coefficient for each parameter and percentile to separate the groups. Kaplan-Meier analysis was used to compare mOS between these groups. Multivariate survival analysis was subsequently conducted. A correlative histopathologic analysis was performed in a subcohort (n = 10) with DTI metrics and rCBVmax on opposite ends of the spectrum. Results: Significant differences in mOS were observed for MDmin (p < 0.05), FA (p < 0.01), CL (p < 0.05), and CP (p < 0.01) and trend toward significance for rCBVmax (p = 0.07) between the two risk groups, in the univariate analysis. On multivariate analysis, the best predictive survival model was comprised of MDmin (p = 0.05), rCBVmax (p < 0.05), RPA (p < 0.0001), and number of lesions (p = 0.07). On histopathology, metastatic tumors showed significant differences in the amount of stroma depending on the combination of DTI metrics and rCBVmax values. Patients with high stromal content demonstrated poorer mOS. Conclusion: Pretreatment DTI-derived parameters, notably MDmin and rCBVmax, are promising imaging markers for prognostication of OS in patients with brain metastases. Stromal cellularity may be a contributing factor to these differences. Advances in knowledge: The correlation of DTI-derived metrics and perfusion MRI with patient outcomes has not been investigated in patients with treatment naïve brain metastasis. DTI and DSC-PWI can aid in therapeutic decision-making by providing additional clinical guidance.

Technological advances in the delivery of radiation and other novel cancer therapies have significantly improved the 5-year survival rates over the last few decades. Although recent developments have helped to better manage the acute effects of radiation, the late effects such as impairment in cognition continue to remain of concern. Accruing data in the literature have implicated derangements in hemodynamic parameters and metabolic activity of the irradiated normal brain as predictive of cognitive impairment. Multiparametric imaging modalities have allowed us to precisely quantify functional and metabolic information, enhancing the anatomic and morphologic data provided by conventional MRI sequences, thereby contributing as noninvasive imaging-based biomarkers of radiation-induced brain injury. In this review, we have elaborated on the mechanisms of radiation-induced brain injury and discussed several novel imaging modalities, including MR spectroscopy, MR perfusion imaging, functional MR, SPECT, and PET that provide pathophysiological and functional insights into the postradiation brain, and its correlation with radiation dose as well as clinical neurocognitive outcomes. Additionally, we explored some innovative imaging modalities, such as quantitative blood oxygenation level-dependent imaging, susceptibility-based oxygenation measurement, and T2-based oxygenation measurement, that hold promise in delineating the potential mechanisms underlying deleterious neurocognitive changes seen in the postradiation setting. We aim that this comprehensive review of a range of imaging modalities will help elucidate the hemodynamic and metabolic injury mechanisms underlying cognitive impairment in the irradiated normal brain in order to optimize treatment regimens and improve the quality of life for these patients.

Superagers are older adults presenting excellent memory performance that may reflect resilience to the conventional pathways of aging. Our contribution aims to shape the evidence body of the known distinctive biomarkers of superagers and their connections with the Brain and Cognitive Reserve and Brain Maintenance concepts. We performed a systematic literature search in PubMed and ScienceDirect with no limit on publication date for studies that evaluated potential biomarkers in superagers classified by validated neuropsychological tests. Methodological quality was assessed using the QUADAS-2 tool. Twenty-one studies were included, the majority in neuroimaging, followed by histological, genetic, cognition, and a single one on blood plasma analysis. Superagers exhibited specific regions of cortical preservation, rather than global cortical maintenance, standing out the anterior cingulate and hippocampus regions. Both superagers and controls showed similar levels of amyloid deposition. Moreover, the functional oscillation patterns in superagers resembled those described in young adults. Most of the quality assessment for the included studies showed medium risks of bias. This systematic review supports selective cortical preservation in superagers, comprehending regions of the default mode, and salience networks, overlapped by stronger functional connectivity. In this context, the anterior cingulate cortex is highlighted as an imaging and histologic signature of these subjects. Besides, the biomarkers included pointed out that the Brain and Cognitive Reserve and Brain Maintenance concepts are independent and complementary in the superagers’ setting.

Objective: To emphasize the most appropriate magnetic resonance imaging (MRI) diffusion protocol for the detection of lesions that cause transient global amnesia, in order to perform an accurate examination, as well as to determine the ideal time point after the onset of symptoms to perform the examination. Materials and Methods: We evaluated five patients with a diagnosis of transient global amnesia treated between 2012 and 2015. We analyzed demographic characteristics, clinical data, symptom onset, diffusion techniques, and radiological findings. Examination techniques included a standard diffusion sequence (b value = 1000 s/mm2; slice thickness = 5 mm) and a optimized diffusion sequence (b value = 2000 s/mm2; slice thickness = 3 mm). Results: Brain MRI was performed at 24 h or 36 h after symptom onset, except in one patient, in whom it was performed at 12 h after (at which point no changes were seen) and repeated at 36 h after symptom onset (at which point it showed alterations in the right hippocampus). The standard and optimized diffusion sequences were both able to demonstrate focal changes in the hippocampi in all of the patients but one, in whom the changes were demonstrated only in the optimized sequence. Conclusion: MRI can confirm a clinical hypothesis of transient global amnesia. Knowledge of the optimal diffusion parameters and the ideal timing of diffusion-weighted imaging (> 24 h after symptom onset) are essential to improving diagnostic efficiency. Resumo Objetivo: Enfatizar o protocolo de difusão mais adequado para detecção de lesões da amnésia global transitória, a fim de realizar um exame preciso, em tempo ideal, após o início dos sintomas. Materiais e Métodos: Foram analisados cinco pacientes com diagnóstico de amnésia global transitória atendidos entre 2012 e 2015, considerando-se dados demográficos, clínicos, tempo do início dos sintomas, técnicas de difusão e achados radiológicos. As técnicas incluíram uma sequência de difusão padrão (b = 1000 s/mm2; espessura do corte = 5 mm) e uma sequência de difusão otimizada (b = 2000 s/mm2; espessura de corte = 3 mm). Resultados: A ressonância magnética de encéfalo foi realizada após 24 ou 36 horas do início dos sintomas, exceto em um paciente, em que foi realizada após 12 horas (sem alterações) e repetida após 36 horas (mostrando alterações hipocampais). Em todos os pacientes foram demonstradas alterações focais na difusão no hipocampo em ambas as técnicas, exceto em um paciente, em que as alterações foram demonstradas apenas na sequência otimizada. Conclusão: A ressonância magnética é capaz de confirmar a hipótese clínica de amnésia global transitória. O conhecimento dos parâmetros ótimos da técnica de difusão e o melhor tempo para a detecção das alterações (> 24 horas) são essenciais para aprimorar a eficiência diagnóstica.

Superagers are older adults presenting excellent memory performance that may reflect resilience to the conventional pathways of aging. Our contribution aims to shape the evidence body of the known distinctive biomarkers of superagers and their connections with the Brain and Cognitive Reserve and Brain Maintenance concepts.We performed a systematic literature search in PubMed and ScienceDirect with no limit on publication date for studies that evaluated potential biomarkers in superagers classified by validated neuropsychological tests. Methodological quality was assessed using the QUADAS-2 tool.Twenty-one studies were included, the majority in neuroimaging, followed by histological, genetic, cognition, and a single one on blood plasma analysis. Superagers exhibited specific regions of cortical preservation, rather than global cortical maintenance, standing out the anterior cingulate and hippocampus regions. Both superagers and controls showed similar levels of amyloid deposition. Moreover, the functional oscillation patterns in superagers resembled those described in young adults. Most of the quality assessment for the included studies showed medium risks of bias.This systematic review supports selective cortical preservation in superagers, comprehending regions of the default mode, and salience networks, overlapped by stronger functional connectivity. In this context, the anterior cingulate cortex is highlighted as an imaging and histologic signature of these subjects. Besides, the biomarkers included pointed out that the Brain and Cognitive Reserve and Brain Maintenance concepts are independent and complementary in the superagers' setting.

There is a broad range of inflammatory, pseudotumoral, and benign lesions that may masquerade as pancreatic malignancies, often representing a challenge to the radiologist. Unawareness of these entities can lead to inadequate differential diagnoses or misdiagnosis, with important prognostic and therapeutic consequences. The purpose of this article is to revisit a spectrum of lesions, varying from common to exceedingly rare nonmalignant, that may mimic malignant pancreatic neoplasms on imaging, identifying relevant features that may contribute to reaching the correct diagnosis. Representative cases include focal fatty replacement, intrapancreatic accessory spleen, pancreatic lobulation, lipoma, autoimmune pancreatitis, focal pancreatitis, eosinophilic pancreatitis, groove pancreatitis, hemangioma, intrapancreatic aneurysm, tuberculosis, and Castleman’s disease.

A 9-day-old girl had, on prenatal ultrasound, brain and cardiac lesions suspicious for tuberous sclerosis. Brain MRI demonstrated a large intraventricular and intraparenchymal mass centered on the foramen of Monro, which had unusual imaging findings: a homogeneous T1-hyperintense and T2-hypointense signal (figure 1, A and B) related to scarce myelination; remarkable venous drainage on susceptibility-weighted imaging (figure 1C); and apparent diffusion coefficient hypointensity, corresponding to blackout T2 effect (figure 2, A and B). Spectroscopy showed increased choline and myo-Inositol peaks (figure 2C). These findings are consistent with neonatal subependymal giant astrocytoma.1,2 Subependymal nodules, cortical tubers, and radial bands were also atypically T1-hyperintense and T2-hypointense (figure 1, A and B).