Suyash Mohan

Differential Diagnosis for Bilateral Abnormalities of the Basal Ganglia and Thalamus

The basal ganglia and thalamus are paired deep gray matter structures that may be involved by a wide variety of disease entities. The basal ganglia are highly metabolically active and are symmetrically affected in toxic poisoning, metabolic abnormalities, and neurodegeneration with brain iron accumulation. Both the basal ganglia and thalamus may be affected by other systemic or metabolic disease, degenerative disease, and vascular conditions. Focal flavivirus infections, toxoplasmosis, and primary central nervous system lymphoma may also involve both deep gray matter structures. The thalamus is more typically affected alone by focal conditions than by systemic disease. Radiologists may detect bilateral abnormalities of the basal ganglia and thalamus in different acute and chronic clinical situations, and although magnetic resonance (MR) imaging is the modality of choice for evaluation, the correct diagnosis can be made only by taking all relevant clinical and laboratory information into account. The neuroimaging diagnosis is influenced not only by detection of specific MR imaging features such as restricted diffusion and the presence of hemorrhage, but also by detection of abnormalities involving other parts of the brain, especially the cerebral cortex, brainstem, and white matter. Judicious use of confirmatory neuroimaging investigations, especially diffusion-weighted imaging, MR angiography, MR venography, and MR spectroscopy during the same examination, may help improve characterization of these abnormalities and help narrow the differential diagnosis.

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

A trial of autologous T cells redirected to a specific mutation in glioblastoma patients illustrates mechanisms of resistance. Speeding toward CAR T cell therapy for glioblastoma Chimeric antigen receptor (CAR) T cells have been successfully implemented for treating leukemia and are now being investigated for solid tumors. O’Rourke et al. conducted a phase 1 safety study of autologous CAR T cells targeted to EGFR variant III in glioblastoma patients. Treatment seemed to be well tolerated, which is critical because other CAR T cell products have been implicated in devastating central nervous system complications. Of the 10 patients enrolled, 7 had surgical intervention, allowing for some analysis of the tumors and T cells in patients’ brains. The results of this trial indicate that CAR T cell therapy is a viable option for treating glioblastoma. We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)–EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up. All patients demonstrated detectable transient expansion of CART-EGFRvIII cells in peripheral blood. Seven patients had post–CART-EGFRvIII surgical intervention, which allowed for tissue-specific analysis of CART-EGFRvIII trafficking to the tumor, phenotyping of tumor-infiltrating T cells and the tumor microenvironment in situ, and analysis of post-therapy EGFRvIII target antigen expression. Imaging findings after CART immunotherapy were complex to interpret, further reinforcing the need for pathologic sampling in infused patients. We found trafficking of CART-EGFRvIII cells to regions of active GBM, with antigen decrease in five of these seven patients. In situ evaluation of the tumor environment demonstrated increased and robust expression of inhibitory molecules and infiltration by regulatory T cells after CART-EGFRvIII infusion, compared to pre–CART-EGFRvIII infusion tumor specimens. Our initial experience with CAR T cells in recurrent GBM suggests that although intravenous infusion results in on-target activity in the brain, overcoming the adaptive changes in the local tumor microenvironment and addressing the antigen heterogeneity may improve the efficacy of EGFRvIII-directed strategies in GBM.

Biologic Imaging of Head and Neck Cancer: The Present and the Future

SUMMARY: While anatomic imaging (CT and MR imaging) of HNC is focused on diagnosing and/or characterizing the disease, defining its local extent, and evaluating distant spread, accurate assessment of the biologic status of the cancer (cellularity, growth rate, response to nonsurgical chemoradiation therapy, and so forth) can be invaluable for prognostication, planning therapy, and follow-up of lesions after therapy. The combination of anatomic and biologic imaging techniques can thus provide a more comprehensive evaluation of the patient. The purpose of this work was to review the present and future clinical applications of advanced biologic imaging techniques in HNC evaluation and management. As part of the biologic imaging array, we discuss MR spectroscopy, diffusion and perfusion MR imaging, CTP, and FDG-PET scanning and conclude with exciting developments that hold promise in assessment of tumor hypoxia and neoangiogenesis.

Differentiating Tumor Progression from Pseudoprogression in Patients with Glioblastomas Using Diffusion Tensor Imaging and Dynamic Susceptibility Contrast MRI

BACKGROUND AND PURPOSE: Early assessment of treatment response is critical in patients with glioblastomas. A combination of DTI and DSC perfusion imaging parameters was evaluated to distinguish glioblastomas with true progression from mixed response and pseudoprogression. MATERIALS AND METHODS: Forty-one patients with glioblastomas exhibiting enhancing lesions within 6 months after completion of chemoradiation therapy were retrospectively studied. All patients underwent surgery after MR imaging and were histologically classified as having true progression (>75% tumor), mixed response (25%–75% tumor), or pseudoprogression (<25% tumor). Mean diffusivity, fractional anisotropy, linear anisotropy coefficient, planar anisotropy coefficient, spheric anisotropy coefficient, and maximum relative cerebral blood volume values were measured from the enhancing tissue. A multivariate logistic regression analysis was used to determine the best model for classification of true progression from mixed response or pseudoprogression. RESULTS: Significantly elevated maximum relative cerebral blood volume, fractional anisotropy, linear anisotropy coefficient, and planar anisotropy coefficient and decreased spheric anisotropy coefficient were observed in true progression compared with pseudoprogression (P < .05). There were also significant differences in maximum relative cerebral blood volume, fractional anisotropy, planar anisotropy coefficient, and spheric anisotropy coefficient measurements between mixed response and true progression groups. The best model to distinguish true progression from non–true progression (pseudoprogression and mixed) consisted of fractional anisotropy, linear anisotropy coefficient, and maximum relative cerebral blood volume, resulting in an area under the curve of 0.905. This model also differentiated true progression from mixed response with an area under the curve of 0.901. A combination of fractional anisotropy and maximum relative cerebral blood volume differentiated pseudoprogression from nonpseudoprogression (true progression and mixed) with an area under the curve of 0.807. CONCLUSIONS: DTI and DSC perfusion imaging can improve accuracy in assessing treatment response and may aid in individualized treatment of patients with glioblastomas.

Imaging of Meningitis and Ventriculitis

Central nervous system infections account for 1% of primary hospital admissions and 2% of nosocomial infections and when encountered require prompt diagnosis and initiation of specific treatment. Imaging findings are mostly nonspecific with respect to the causative pathogen. This article describes the anatomy of cranial meninges and extra-axial spaces of the brain. Characteristic findings and recent advances in neuroimaging of meningitis and its complications and ventriculitis are summarized, and certain noninfectious causes of meningitis and meningitis mimics are described.

Diagnostic utility of diffusion tensor imaging in differentiating glioblastomas from brain metastases.

BACKGROUND AND PURPOSE: Differentiation of glioblastomas and solitary brain metastases is an important clinical problem because the treatment strategy can differ significantly. The purpose of this study was to investigate the potential added value of DTI metrics in differentiating glioblastomas from brain metastases. MATERIALS AND METHODS: One hundred twenty-eight patients with glioblastomas and 93 with brain metastases were retrospectively identified. Fractional anisotropy and mean diffusivity values were measured from the enhancing and peritumoral regions of the tumor. Two experienced neuroradiologists independently rated all cases by using conventional MR imaging and DTI. The diagnostic performances of the 2 raters and a DTI-based model were assessed individually and combined. RESULTS: The fractional anisotropy values from the enhancing region of glioblastomas were significantly higher than those of brain metastases (P < .01). There was no difference in mean diffusivity between the 2 tumor types. A classification model based on fractional anisotropy and mean diffusivity from the enhancing regions differentiated glioblastomas from brain metastases with an area under the receiver operating characteristic curve of 0.86, close to those obtained by 2 neuroradiologists using routine clinical images and DTI parameter maps (area under the curve = 0.90 and 0.85). The areas under the curve of the 2 radiologists were further improved to 0.96 and 0.93 by the addition of the DTI classification model. CONCLUSIONS: Classification models based on fractional anisotropy and mean diffusivity from the enhancing regions of the tumor can improve diagnostic performance in differentiating glioblastomas from brain metastases.

Contrast-enhanced magnetic resonance angiography.

Magnetic resonance (MR) angiography is a powerful tool for the evaluation of cervical and intracranial vasculature. Both noncontrast and contrast-enhanced MR angiography can provide exquisite vascular contrast and detail without the use of ionizing radiation. More advanced techniques such as time-resolved MR angiography and parallel imaging provide dynamic information in rapid fashion. This article describes the basic principles and techniques of MR angiography image acquisition.

Advances in Multiple Sclerosis and its Variants: Conventional and Newer Imaging Techniques

Multiple sclerosis (MS) and its variants are inflammatory as well as neurodegenerative diseases that diffusely affect the central nervous system (CNS). There is a poor correlation between traditional imaging findings and symptoms in patients with MS. Current research in conventional magnetic resonance (MR) imaging of MS and related diseases includes optimization of hardware and pulse sequences and the development of automated and semiautomated techniques to measure and quantify disease burden. Advanced nonconventional MR techniques such as diffusion tensor and functional MR imaging probe the changes found in the CNS, and correlate these findings with clinical measures of disease.

Prognostic Value of Dynamic Susceptibility Contrast-Enhanced and Diffusion-Weighted MR Imaging in Patients with Glioblastomas

BACKGROUND AND PURPOSE: Prediction of survival in patients with glioblastomas is important for individualized treatment planning. This study aimed to assess the prognostic utility of presurgical dynamic susceptibility contrast and diffusion-weighted imaging for overall survival in patients with glioblastoma. MATERIALS AND METHODS: MR imaging data from pathologically proved glioblastomas between June 2006 to December 2013 in 58 patients (mean age, 62.7 years; age range, 22–89 years) were included in this retrospective study. Patients were divided into long survival (≥15 months) and short survival (<15 months) groups, depending on overall survival time. Patients underwent dynamic susceptibility contrast perfusion and DWI before surgery and were treated with chemotherapy and radiation therapy. The maximum relative cerebral blood volume and minimum mean diffusivity values were measured from the enhancing part of the tumor. RESULTS: Maximum relative cerebral blood volume values in patients with short survival were significantly higher compared with those who demonstrated long survival (P < .05). No significant difference was observed in the minimum mean diffusivity between short and long survivors. Receiver operator curve analysis demonstrated that a maximum relative cerebral blood volume cutoff value of 5.79 differentiated patients with low and high survival with an area under the curve of 0.93, sensitivity of 0.89, and specificity of 0.90 (P < .001), while a minimum mean diffusivity cutoff value of 8.35 × 10−4mm2/s had an area under the curve of 0.55, sensitivity of 0.71, and specificity of 0.47 (P > .05) in separating the 2 groups. CONCLUSIONS: Maximum relative cerebral blood volume may be used as a prognostic marker of overall survival in patients with glioblastomas.

Transoral Robotic Surgery in Head and Neck Cancer: What Radiologists Need to Know about the Cutting Edge

The evolution of oncologic surgical technology has moved toward reducing patient morbidity and mortality without compromising oncologic resection or oncologic outcomes. The goals in treating head and neck cancer are to cure patients, as well as to provide quality of life by improving functional and social outcomes through organ-preservation therapies, which may include surgery, chemotherapy, and/or radiation therapy. Transoral robotic surgery (TORS) is an emerging technique that provides several benefits over existing treatment regimens and over open surgery for head and neck cancer, including reductions in operative times, blood loss, intensive care unit stays, and overall duration of patient hospitalization. Transoral robotic techniques allow wide-view, high-resolution, magnified three-dimensional optics for visualization of the mucosal surfaces of the head and neck through an endoscope, while avoiding the extensive external cervical incisions often required for open surgeries. Radiologists play an important role in the successful outcome of these procedures, both before and after TORS. Determining a cancer patients surgical candidacy for TORS requires a thorough preoperative radiologic evaluation, coupled with clinical and intraoperative assessment. Radiologists must pay particular attention to important anatomic landmarks that are clinical blind spots for surgeons. Knowledge of the expected postoperative imaging appearances, so that they can be distinguished from recurrent disease and second primary tumors, is essential for all radiologists involved in the care of these patients.