Girish Fatterpekar

Treatment-related change versus tumor recurrence in high-grade gliomas: a diagnostic conundrum--use of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI.

OBJECTIVEnThe purpose of this article is to address radiation necrosis, pseudoprogression, and pseudoresponse relative to high-grade gliomas and evaluate the role of conventional MRI and, in particular, dynamic susceptibility contrast-enhanced perfusion MRI in assessing such treatment-related changes from tumor recurrence.nnnCONCLUSIONnPosttreatment imaging assessment of high-grade gliomas remains challenging. Familiarity with the expected MR imaging appearances of treatment-related change and tumor recurrence will help distinguish these entities allowing appropriate management.

Mutant IDH1 and thrombosis in gliomas

Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II–IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26–30xa0% of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0xa0%). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85–90xa0% in wild-type versus 2–6xa0% in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

Comparison of Perfusion, Diffusion, and MR Spectroscopy between Low-Grade Enhancing Pilocytic Astrocytomas and High-Grade Astrocytomas

BACKGROUND AND PURPOSE: The differentiation of pilocytic astrocytomas and high-grade astrocytomas is sometimes difficult. There are limited comparisons in the literature of the advanced MR imaging findings of pilocytic astrocytomas versus high-grade astrocytomas. The purpose of this study was to assess the MR imaging, PWI, DWI, and MR spectroscopy characteristics of pilocytic astrocytomas compared with high-grade astrocytomas. MATERIALS AND METHODS: Sixteen patients with pilocytic astrocytomas and 22 patients with high-grade astrocytomas (8–66 years of age; mean, 36 ± 17 years) were evaluated by using a 1.5T MR imaging unit. MR imaging, PWI, DWI, and MR spectroscopy were used to determine the differences between pilocytic astrocytomas and high-grade astrocytomas. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined. RESULTS: The relative cerebral blood volume values were significantly lower in pilocytic astrocytomas compared with the high-grade astrocytomas (1.4 ± 0.9 versus 3.3 ± 1.4; P = .0008). The ADC values were significantly higher in pilocytic astrocytomas compared with high-grade astrocytomas (1.5 × 10−3 ± 0.4 versus 1.2 × 10−3 ± 0.3; P = .01). The lipid-lactate in tumor/creatine in tumor ratios were significantly lower in pilocytic astrocytomas compared with high-grade astrocytomas (8.3 ± 11.2 versus 43.3 ± 59.2; P = .03). The threshold values ≥1.33 for relative cerebral blood volume provide sensitivity, specificity, positive predictive values, and negative predictive values of 100%, 67%, 87%, and 100%, respectively, for differentiating high-grade astrocytomas from pilocytic astrocytomas. The optimal threshold values were ≤1.60 for ADC, ≥7.06 for lipid-lactate in tumor/creatine in tumor, and ≥2.11 for lipid-lactate in tumor/lipid-lactate in normal contralateral tissue. CONCLUSIONS: Lower relative cerebral blood volume and higher ADC values favor a diagnosis of pilocytic astrocytoma, while higher lipid-lactate in tumor/creatine in tumor ratios plus necrosis favor a diagnosis of high-grade astrocytomas.

Prevalence of radiographic semicircular canal dehiscence in very young children: an evaluation using high-resolution computed tomography of the temporal bones

AbstractBackgroundPrevious studies suggest that semicircular canal dehiscences (SCDs) have a developmental origin.ObjectiveWe hypothesized that if SCDs originate during development, incidence of radiographic SCDs in young children will be higher than in adults.Materials and methodsThirty-four temporal bone HRCTs of children younger than 2xa0years and 40 temporal bone HRCTs of patients older than 18xa0years were reformatted and re-evaluated for presence of SCD or canal thinning. Results were compared with indications for HRCT and clinical information.ResultsSCDs were detected in 27.3% of children younger than 2xa0years of age (superior, 13.8%; posterior, 20%) and in 3% of adults (Pu2009n <u20090.004). Of children with one radiographic dehiscence, 55.6% had multiple and 44% had bilateral SCDs on HRCT. No lateral canal SCDs were present. Thinning of bone overlying the semicircular canals was found in 44% of children younger than 2xa0years and 2.5% of adults (Pu2009<u20090.0001).ConclusionSCDs are more common on HRCTs of very young children. This supports the hypothesis that SCDs originate from discontinuation of bone deposition/maturation. However, SCDs on imaging do not necessarily correlate with canal dehiscence syndrome and should therefore be interpreted carefully.

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy

Track density imaging (TDI) is a novel MR imaging postprocessing technique based on high angular-resolution diffusion acquisitions that generate super-resolution images derived by whole-brain probabilistic streamline tractography. TDI and echo modulation curve T2 mapping were combined with simultaneous multisection acquisition to reveal anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. SUMMARY: Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization.

High-Resolution DCE-MRI of the Pituitary Gland Using Radial k-Space Acquisition with Compressed Sensing Reconstruction

BACKGROUND AND PURPOSE: The pituitary gland is located outside of the blood-brain barrier. Dynamic T1 weighted contrast enhanced sequence is considered to be the gold standard to evaluate this region. However, it does not allow assessment of intrinsic permeability properties of the gland. Our aim was to demonstrate the utility of radial volumetric interpolated brain examination with the golden-angle radial sparse parallel technique to evaluate permeability characteristics of the individual components (anterior and posterior gland and the median eminence) of the pituitary gland and areas of differential enhancement and to optimize the study acquisition time. MATERIALS AND METHODS: A retrospective study was performed in 52 patients (group 1, 25 patients with normal pituitary glands; and group 2, 27 patients with a known diagnosis of microadenoma). Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were evaluated with an ROI-based method to obtain signal-time curves and permeability measures of individual normal structures within the pituitary gland and areas of differential enhancement. Statistical analyses were performed to assess differences in the permeability parameters of these individual regions and optimize the study acquisition time. RESULTS: Signal-time curves from the posterior pituitary gland and median eminence demonstrated a faster wash-in and time of maximum enhancement with a lower peak of enhancement compared with the anterior pituitary gland (P < .005). Time-optimization analysis demonstrated that 120 seconds is ideal for dynamic pituitary gland evaluation. In the absence of a clinical history, differences in the signal-time curves allow easy distinction between a simple cyst and a microadenoma. CONCLUSIONS: This retrospective study confirms the ability of the golden-angle radial sparse parallel technique to evaluate the permeability characteristics of the pituitary gland and establishes 120 seconds as the ideal acquisition time for dynamic pituitary gland imaging.

Noninvasive diagnosis and management of spontaneous intracranial hypotension in patients with marfan syndrome: Case Report and Review of the Literature.

Background: Spontaneous intracranial hypotension is an uncommon clinical entity. Heritable connective tissue disorders (HCTD), such as Marfan syndrome, are frequently implicated as an underlying cause, due to dural structural weaknesses that predispose patients to spontaneous cerebrospinal fluid (CSF) leak. Due to the high prevalence of multi-system disease in HCTD, diagnosis and treatment are often complicated. Case Description: We present a 58-year-old female with Marfan syndrome on anticoagulation for a mechanical aortic valve replacement who came to medical attention with severe, acute-onset headache following a straining episode. Noninvasive magnetic resonance (MR) myelography confirmed thoracic CSF extravasations and multiple lumbar diverticula. The patient was treated conservatively and her symptoms resolved. Conclusion: We discuss the common presentation, diagnostic tools, and treatment options for spontaneous CSF leaks in patients with Marfan syndrome or related HCTD with an emphasis on noninvasive modalities and a review of the major radiographic criteria used to diagnose dural abnormalities, such as dural ectasia.

Head and Neck MRI Findings in CHARGE Syndrome

SUMMARY: Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and deafness (CHARGE) syndrome is a disorder with multiple congenital anomalies seen on imaging. A retrospective review of 10 patients with CHARGE syndrome who underwent MR imaging of the brain as part of a preoperative evaluation for cochlear implantation was conducted. Structural abnormalities of the entire MR imaging of the head were evaluated, including the auditory system, olfactory system, face, skull base, and central nervous system. The most frequent MR imaging findings included dysplasias of the semicircular canals and hypoplasia of the frontal lobe olfactory sulci. Less frequent findings included cleft lip/palate and coloboma. Our study uncovered new findings of a J-shaped sella, dorsal angulation of the clivus, and absent/atrophic parotid glands, not previously described in patients with CHARGE. Our results emphasize the utility of MR imaging in the diagnosis and management of patients with CHARGE syndrome.

Diseases of the Sella and Parasellar Region: An Overview

The central skull base is formed by the posterior aspect of the presphenoid anteriorly, the basisphenoid centrally, the greater wings of sphenoid laterally, and the dorsum sella and petrous ridges posteriorly. The sella turcica is a saddleshaped depression in the basisphenoid and houses the pituitary gland.1 The pituitary gland largely consists of 2 parts: the anterior pituitary or adenohypophysis, and posterior pituitary or neurohypophysis. The adenohypophysis starts as an evagination of the primitive fetal oral ectoderm (or Rathke’s pouch) that migrates from the roof of the primitive oral cavity superiorly into the middle cranial fossa to form the adenohypophysis.2 Majority of the anterior pituitary develops from the anterior wall of the Rathke’s pouch. The neurohypophysis, in turn, forms as an outgrowth of the diencephalon. Subsequently, the anterior and posterior lobes fuse to form the normal pituitary gland, and the Rathke’s pouch regresses. Abnormal persistence and enlargement of the Rathke’s cleft (Rathke’s pouch remnant) results in Rathke cleft cyst (RCC).3 The anterior pituitary is made up of 3 parts: the pars tuberalis, pars intermedia, and pars distalis. The pars tuberalis is a small amount of adenohypophyseal tissue that wraps anteriorly along the pituitary stalk. The pars distalis forms the main body of the anterior pituitary. It produces multiple hormones, including the growth hormone, adrenocortico-

Parotid Gland Atrophy in Patients with Chronic Trigeminal Nerve Denervation

BACKGROUND AND PURPOSE: Trigeminal nerve injury or dysfunction is associated with denervation atrophy of muscles innervated by the mandibular branch of the trigeminal nerve. The purpose of our study was to evaluate the association between chronic CN V denervation and parotid gland atrophy. MATERIALS AND METHODS: Twenty-six patients with chronic masticator muscle atrophy were retrospectively identified and evaluated for the presence of ipsilateral parotid gland atrophy. Twenty-six age-matched control subjects with no clinical or imaging evidence of chronic masticator space atrophy were also identified. Segmentation of the parotid gland was performed to calculate a parotid asymmetry index. The Fisher exact test and t test were respectively used to determine the correlation between parotid gland atrophy and ipsilateral masticator muscle atrophy and to evaluate any difference in the size of the involved parotid gland when compared with that in the control subjects. RESULTS: Ipsilateral parotid gland atrophy was seen in 9/26 (42.8%) patients with fatty replacement of the masticator group of muscles, suggesting a correlation between parotid gland atrophy and CN V denervation (P < .001). The parotid asymmetry index was significantly different in patients with CN V denervation (0.59 ± 0.25) compared with control subjects (0.92 ± 0.03) (P < .001). CONCLUSIONS: Ipsilateral parotid gland atrophy can accompany chronic CN V denervation change, and its clinical significance remains to be determined.