Magnetic Resonance Imaging in the Contemporary Management of Medulloblastoma: Current and Emerging Applications.

Medulloblastoma, the most common malignant primary brain tumor in children, is now considered to comprise of four distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4 medulloblastoma, each associated with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and variable clinical behavior. Due to its exquisite anatomic resolution, multiparametric nature, and ability to image the entire craniospinal axis, magnetic resonance imaging (MRI) is the preferred and recommended first-line imaging modality for suspected brain tumors including medulloblastoma. Preoperative MRI can reliably differentiate medulloblastoma from other common childhood posterior fossa masses such as ependymoma, pilocytic astrocytoma, and brainstem glioma. On T1-weighted images, medulloblastoma is generally iso- to hypointense, while on T2-weighted images, the densely packed cellular component of the tumor is significantly hypointense and displays restricted diffusion on diffusion-weighted imaging. Following intravenous gadolinium, medulloblastoma shows significant but variable and heterogeneous contrast enhancement. Given the propensity of neuraxial spread in medulloblastoma, sagittal fat-suppressed T1-postcontrast spinal MRI is recommended to rule out leptomeningeal metastases for accurate staging. Following neurosurgical excision, postoperative MRI done within 24-48 h confirms the extent of resection, accurately quantifying residual tumor burden imperative for risk assignment. Post-treatment MRI is needed to assess response and effectiveness of adjuvant radiotherapy and systemic chemotherapy. After completion of planned therapy, surveillance MRI is recommended periodically on follow-up for early detection of recurrence for timely institution of salvage therapy, as well as for monitoring treatment-related late complications. Recent studies suggest that preoperative MRI can reliably identify SHH and Group 4 medulloblastoma but has suboptimal predictive accuracy for WNT and Group 3 tumors. In this review, we focus on the role of MRI in the diagnosis, staging, and quantifying residual disease; post-treatment response assessment; and periodic surveillance, and provide a brief summary on radiogenomics in the contemporary management of medulloblastoma.

Prognostic impact of semantic MRI features on survival outcomes in molecularly subtyped medulloblastoma.

PURPOSE: Imaging features are known to reflect inherent disease biology in various cancers including brain tumors. We report on the prognostic impact of magnetic resonance imaging (MRI) features on survival in patients with medulloblastoma treated between 2007 and 2018 at our institute. METHODS: Sixteen semantic imaging features (with predefined categories) were extracted from pre- and postcontrast T1-weighted and T2-weighted MRI by consensus. Univariate analysis and multivariate Cox regression analysis were performed to assess the correlation of semantic features with relapse-free survival (RFS) and overall survival (OS). RESULTS: The study cohort comprised 171 medulloblastoma patients (median age 9 years) treated with maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. A total of 55 patients experienced recurrent/progressive disease (commonly neuraxial metastases) resulting in 44 deaths, including one treatment-related death. At a median follow-up of 45 months (interquartile range 19-65 months), 5­year Kaplan-Meier estimates of RFS and OS were 64% and 71%, respectively. Semantic MRI features such as non-central tumor location on vertical axis, absence of brainstem involvement, ≤ 80% solid tumor area with contrast uptake, heterogenous pattern of contrast enhancement, necrosis, calcification, and T2-weighted heterogeneity were associated with significantly worse RFS and/or OS in univariate analysis. Cox regression analysis identified tumor location on the vertical axis, brainstem involvement, and calcification as independent prognostic factors impacting outcomes. Distinctive MRI features correlated with survival even within individual molecular subgroups of medulloblastoma. CONCLUSION: Distinctive semantic MRI features correlate significantly with survival outcomes in medulloblastoma, also within individual molecular subgroups, reflecting their prognostic impact.

A case report of Arnold Chiari type 1 malformation in acromesomelic dwarf infant.

Arnold Chiari malformation is one of the commonest cause of congenital hydrocephalus. Cause of fetal development of cerebellar tonsils remains unknown and may be diagnosed at later in life. The association of Arnold Chiari malformation with acromesomelic dwarfism is not known. We report male infant diagnosed with acromesomelic dwarfism at end of gestation period on basis of antenatal ultrasonography findings. An ultrasound scan of infant head at fifth month of birth was performed in view of increasing head circumference that revealed aqueductal stenosis with dilated posterior horn of lateral ventricles in brain.

Nomograms based on preoperative multiparametric magnetic resonance imaging for prediction of molecular subgrouping in medulloblastoma: results from a radiogenomics study of 111 patients.

Background: Novel biological insights have led to consensus classification of medulloblastoma into 4 distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We aimed to predict molecular subgrouping in medulloblastoma based on preoperative multiparametric magnetic resonance imaging (MRI) characteristics. Methods: A set of 19 MRI features were evaluated in 111 patients with histologic diagnosis of medulloblastoma for prediction of molecular subgrouping. MRI characteristics were correlated with molecular subgroups derived from tissue samples in 111 patients (WNT = 17, SHH = 44, Group 3 = 27, and Group 4 = 23). Multinomial logistic regression of imaging parameters was performed on a training cohort (TC) of 76 patients, representing two-thirds of randomly selected patients from each of 4 molecular subgroups, to generate binary nomograms. Validation of these nomograms was performed on the remaining 35 patients as the validation cohort (VC). Results: Medulloblastoma subgroups could be accurately predicted by preoperative MRI features in 74% of cases. Predictive accuracy was excellent for SHH (95%), acceptably high for Group 4 (78%), modest for Group 3 (56%) and worst for WNT (41%) subgroup medulloblastoma. SHH-specific nomogram was associated with excellent correlation between TC and VC, with area under the curve (AUC) of 0.939 and 0.991, respectively. AUC for Group 4 was acceptable at 0.851 and 0.788 in TC and VC, respectively; however, these values were consistently suboptimal in WNT and Group 3 medulloblastoma. Conclusion: The predictive accuracy of MRI-based nomograms was excellent for SHH and encouraging for Group 4 medulloblastoma. Further work is needed for Group 3 and WNT-pathway medulloblastoma.

Indian Society of Neuro-Oncology consensus guidelines for the contemporary management of medulloblastoma.

INTRODUCTION: The high success rate in the management medulloblastoma achieved in the western world is not exactly mirrored in developing countries including India. Socio-demographic differences, health-care disparity, and lack in uniformity of care with resultant widespread variations in the clinical practice are some of the reasons that may partly explain this difference in outcomes. Patients with medulloblastoma require a multi-disciplinary team approach involving but not limited to neuro-radiology, neurosurgery; neuropathology, molecular biology, radiation oncology, pediatric medical oncology and rehabilitative services for optimizing outcomes. METHODS: The Indian Society of Neuro-Oncology (ISNO) constituted an expert multi-disciplinary panel with adequate representation from all stakeholders to prepare national consensus guidelines for the contemporary management of medulloblastoma. RESULTS: Minimum desirable, as well as preferable though optional recommendations (as appropriate), were developed and adopted for the pre-surgical work-up including neuroimaging; neurosurgical management including surgical principles, techniques, and complications; neuropathology reporting and molecular testing; contemporary risk-stratification in the molecular era; appropriate adjuvant therapy (radiotherapy and chemotherapy); and follow-up schedule in medulloblastoma. CONCLUSIONS: The current document represents a broad consensus reached amongst various stakeholders within the neuro-oncology community involved in the contemporary curative-intent management of children with medulloblastoma. It provides both general as well as specific guidelines and recommendations to be adopted by physicians and health care providers across India to achieve uniformity of care, improve disease-related outcomes, and compare results between institutions within the country.

Which is the most optimal technique to spare hippocampus?-Dosimetric comparisons of SCRT, IMRT, and tomotherapy.

AIMS: To evaluate current focal high precision radiotherapy (RT) techniques to spare hippocampi most optimally, in view of mounting clinical evidence to preserve neurocognition. MATERIALS AND METHODS: Computed tomography/magnetic resonance imaging (CT/MRI) datasets of 10 patients with benign/low-grade brain tumors, treated with focal conformal RT were replanned with helical tomotherapy (Tomo), intensity-modulated radiotherapy (IMRT) with high definition multileaf collimator (HD-MLC), and forward planning stereotactic conformal radiotherapy (SCRT). The primary planning objective was to encompass 99% of planning target volume (PTV) by 95% of prescribed dose (54 Gy/30#). Assessments included target coverage (TC), homogeneity index (HI), and maximum (max) and minimum (min) dose. Hippocampal dose was assessed with mean, maximum, minimum, median dosem and various dose levels. RESULTS: Mean V 95 for PTV coverage in Tomo, IMRT, and SCRT were 99.7, 99.4, and 98.3%, respectively. PTV coverage was significantly better in Tomo and IMRT compared to SCRT (P = 0.03). Tomotherapy (HI ≤ 0.06) and IMRT (HI ≤ 0.06) plans were more homogenous than SCRT (HI > 0.7) (P = 0.00). Right hippocampus mean dose with Tomo (20Gy) was 18.5% less than SCRT (30 Gy); but for left hippocampus, difference decreased to 3.3% (Tomo-32.2Gy and SCRT-34Gy). At 30% dose level, 9% more volume of right hippocampus was treated in IMRT and 20% in SCRT when compared to Tomo plan. At 80% dose, 6 and 12% more volumes were treated with IMRT and SCRT, respectively, in comparison to Tomo plan. For left hippocampus all three techniques were comparable. CONCLUSION: Tomotherapy and Linear accelerator (LINAC)-based IMRT achieved significantly better PTV coverage than forward planned SCRT. Tomo as compared to SCRT and IMRT plans showed trend towards significant sparing of the contralateral hippocampus, in eccentrically located tumors.

Magnesium deposition in brain of pregnant patients administered intramuscular magnesium sulphate.

We present three cases of T1 hyperintense signal in the MRI scans of the brains of pregnant patients who were administered magnesium sulphate intramuscularly for control of hypertension during eclampsia. The increase in signal is symmetric and is seen in the globus pallidi of these patients. We postulate it to be secondary to deposition of magnesium in the brain parenchyma. The signal intensity was found to be directly varying according to the level of magnesium in the blood. It decreased over a period of time coming to normalcy after approximately 6months. To the best of our knowledge, this is the first case report which has documented this finding. It has to be determined whether deposition of magnesium in the brain parenchyma could have implications in the use of magnesium sulphate in pregnant patients.

Pictorial essay: Role of magnetic resonance imaging in evaluation of brachial plexus pathologies.

Brachial plexopathies, traumatic and nontraumatic, often present with vague symptoms. Clinical examination and electrophysiological studies are useful but may not localize the lesion accurately. Magnetic resonance imaging (MRI) with its multiplanar imaging capability and soft tissue contrast resolution plays an important role in evaluation of the abnormal brachial plexus.

Accurate prostate volume estimation using multifeature active shape models on T2-weighted MRI.

RATIONALE AND OBJECTIVES: Accurate prostate volume estimation is useful for calculating prostate-specific antigen density and in evaluating posttreatment response. In the clinic, prostate volume estimation involves modeling the prostate as an ellipsoid or a spheroid from transrectal ultrasound, or T2-weighted magnetic resonance imaging (MRI). However, this requires some degree of manual intervention, and may not always yield accurate estimates. In this article, we present a multifeature active shape model (MFA) based segmentation scheme for estimating prostate volume from in vivo T2-weighted MRI. MATERIALS AND METHODS: We aim to automatically determine the location of the prostate boundary on in vivo T2-weighted MRI, and subsequently determine the area of the prostate on each slice. The resulting planimetric areas are aggregated to yield the volume of the prostate for a given patient. Using a set of training images, the MFA learns the most discriminating statistical texture descriptors of the prostate boundary via a forward feature selection algorithm. After identification of the optimal image features, the MFA is deformed to accurately fit the prostate border. An expert radiologist segmented the prostate boundary on each slice and the planimetric aggregation of the enclosed areas yielded the ground truth prostate volume estimate. The volume estimation obtained via the MFA was then compared against volume estimations obtained via the ellipsoidal, Myschetzky, and prolated spheroids models. RESULTS: We evaluated our MFA volume estimation method on a total 45 T2-weighted in vivo MRI studies, corresponding to both 1.5 Tesla and 3.0 Tesla field strengths. The results revealed that the ellipsoidal, Myschetzky, and prolate spheroid models overestimated prostate volumes, with volume fractions of 1.14, 1.53, and 1.96, respectively. By comparison, the MFA yielded a mean volume fraction of 1.05, evaluated using a fivefold cross-validation scheme. A correlation with the ground truth volume estimations showed that the MFA had an r(2) value of 0.82, whereas the clinical volume estimation schemes had a maximum value of 0.70. CONCLUSIONS: Our MFA scheme involves minimal user intervention, is computationally efficient and results in volume estimations more accurate than state of the art clinical models.

A magnetic resonance spectroscopy driven initialization scheme for active shape model based prostate segmentation.

Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculation of prostate volume pre- and post-treatment, to detect extra-capsular spread, and for creating patient-specific anatomical models. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter- and intra-reader variability. T2-weighted (T2-w) magnetic resonance (MR) structural imaging (MRI) and MR spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. MRS data consists of spectral signals measuring relative metabolic concentrations, and the metavoxels near the prostate have distinct spectral signals from metavoxels outside the prostate. Active Shape Models (ASM's) have become very popular segmentation methods for biomedical imagery. However, ASMs require careful initialization and are extremely sensitive to model initialization. The primary contribution of this paper is a scheme to automatically initialize an ASM for prostate segmentation on endorectal in vivo multi-protocol MRI via automated identification of MR spectra that lie within the prostate. A replicated clustering scheme is employed to distinguish prostatic from extra-prostatic MR spectra in the midgland. The spatial locations of the prostate spectra so identified are used as the initial ROI for a 2D ASM. The midgland initializations are used to define a ROI that is then scaled in 3D to cover the base and apex of the prostate. A multi-feature ASM employing statistical texture features is then used to drive the edge detection instead of just image intensity information alone. Quantitative comparison with another recent ASM initialization method by Cosio showed that our scheme resulted in a superior average segmentation performance on a total of 388 2D MRI sections obtained from 32 3D endorectal in vivo patient studies. Initialization of a 2D ASM via our MRS-based clustering scheme resulted in an average overlap accuracy (true positive ratio) of 0.60, while the scheme of Cosio yielded a corresponding average accuracy of 0.56 over 388 2D MR image sections. During an ASM segmentation, using no initialization resulted in an overlap of 0.53, using the Cosio based methodology resulted in an overlap of 0.60, and using the MRS-based methodology resulted in an overlap of 0.67, with a paired Student's t-test indicating statistical significance to a high degree for all results. We also show that the final ASM segmentation result is highly correlated (as high as 0.90) to the initialization scheme.

Multi-attribute non-initializing texture reconstruction based active shape model (MANTRA).

In this paper we present MANTRA (Multi-Attribute, Non-Initializing, Texture Reconstruction Based Active Shape Model) which incorporates a number of features that improve on the the popular Active Shape Model (ASM) algorithm. MANTRA has the following advantages over the traditional ASM model. (1) It does not rely on image intensity information alone, as it incorporates multiple statistical texture features for boundary detection. (2) Unlike traditional ASMs, MANTRA finds the border by maximizing a higher dimensional version of mutual information (MI) called combined MI (CMI), which is estimated from kNN entropic graphs. The use of CMI helps to overcome limitations of the Mahalanobis distance, and allows multiple texture features to be intelligently combined. (3) MANTRA does not rely on the mean pixel intensity values to find the border; instead, it reconstructs potential image patches, and the image patch with the best reconstruction based on CMI is considered the object border. Our algorithm was quantitatively evaluated against expert ground truth on almost 230 clinical images (128 1.5 Tesla (T) T2 weighted in vivo prostate magnetic resonance (MR) images, 78 dynamic contrast enhanced breast MR images, and 21 3T in vivo T1-weighted prostate MR images) via 6 different quantitative metrics. Results from the more difficult prostate segmentation task (in which a second expert only had a 0.850 mean overlap with the first expert) show that the traditional ASM method had a mean overlap of 0.668, while the MANTRA model had a mean overlap of 0.840.

Antenatal diagnosis of iniencephaly: sonographic and MR correlation: a case report.

Iniencephaly is an uncommon and fatal neural tube defect involving the occiput and inion, this occurs together with rachischisis of the cervical and thoracic spine, and retroflexion of the head. We report the ultrasound (US) and magnetic resonance (MR) imaging findings of a case of iniencephaly with clubfeet and arthrogryposis. The diagnosis of iniencephaly is easy to make on ultrasound due to the typical star-gazing fetus. However, the details of the fetal brain and spinal cord may not be adequately delineated on US. We found MR imaging to be superior for depicting central nervous system abnormalities. MR imaging has evolved as an imaging modality and it is complementary to fetal US, yet US remains the screening modality of choice.

MRI diagnosis of hypertrophic osteoarthropathy from a remote childhood malignancy.

Hypertrophic osteoarthropathy (HOA) is a clinico-radiological syndrome characterized by digital clubbing, periosteal proliferation, bone pain, synovitis and arthralgia, all of these being commonly symmetrical. It is occasionally associated with nasopharyngeal lymphoepitheliomas and may develop before or after development of lung metastases in these patients. We report a case of a healthy 22-year-old female who presented to our institution with pain and swelling in the thighs and legs. She had a history of childhood nasopharyngeal lymphoepithelioma. Radiographs of the knees were negative. Magnetic resonance imaging (MRI) showed features suggestive of bilateral periostitis. Because of the propensity of the rare childhood nasopharyngeal lymphoepithelioma to present with HOA, this entity was included in the differential diagnosis. A subsequent chest radiograph and CT demonstrated a lung and mediastinal mass that were histologically confirmed to be metastatic. To the best of our knowledge, HOA and metastases from nasopharyngeal lymphoepithelioma occurring after such a long time interval have not been previously reported. Early demonstration and consideration of HOA on the basis of MRI, lead to expeditious and appropriate subsequent investigation.

Pre- and post-therapy MR imaging in fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva, also known as myositis ossificans progressiva, is characterized by congenital skeletal malformations and progressive ectopic bone formation in connective tissues. The disorder presents as rapidly growing masses usually in the neck or paraspinal region with stiffness in the adjoining joints. The preosseous lesions involve the fascia, ligaments, tendons, and skeletal muscle. These lesions occasionally resolve but more often progress to form ectopic ossification. We present a boy who had a characteristic clinical presentation. Magnetic resonance (MR) imaging conducted in the preosseous stage of the lesion revealed the pathology, resulting in early therapy and resolution of the preosseous lesion without progression to ossification. To the best of our knowledge, post-therapy follow-up MR imaging in such a case has not been reported.

Regression of white matter hypodensities with age in Aicardi-Goutierés syndrome: a case report.

BACKGROUND: Aicardi-Goutierés syndrome (AGS) is a severe and progressive familial encephalopathy that is characterized by acquired microcephaly, intracranial calcification, white matter lesions, and chronic lymphocytosis with elevated levels of interferon-alpha in the cerebrospinal fluid. Although the degree of calcification and the severity of brain atrophy are variable, typically, the brain lesions appear to progress on successive examinations. CASE REPORT: We report a 7-year-old male patient who showed relative regression of white matter lesions with nonprogression of basal ganglia calcification and atrophy on follow-up magnetic resonance imaging and computed tomography scans. RESULTS: Magnetic resonance spectroscopy findings were normal. This, to our knowledge, is the first case report, which describes relative regression of the white matter changes in AGS.