What’s New in Neuroimaging – July 2021

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Retinoblastoma: What the Neuroradiologist Needs to Know

V.M. Silvera, J.B. Guerin, W. Brinjikji, and L.A. Dalvin

American Journal of Neuroradiology; January 2021

This review article discusses the clinical presentation of retinoblastoma, ophthalmic imaging modalities, neuroradiology imaging features, and current treatment options with special emphasis on what the neuroradiologist should know. The neuroradiologist is involved in diagnosis, staging, treatment (e.g. intra-arterial chemotherapy), and follow-up.

Retinoblastoma originates in the retina and can display; endophytic growth into the vitreous chamber; exophytic growth into the sub-retinal space; and diffuse, infiltrative growth along the retina.

Multiple imaging modalities are discussed with neuroradiology primarily driven by MRI to evaluate optic nerve invasion, extraocular tumor extension, and intracranial disease. CT in the evaluation of retinoblastoma is now considered obsolete as there is potential risk of developing secondary cancers from ionizing radiation exposure (especially in germline retinoblastoma) while providing no additional value over ultrasound for detection of calcification.

On MR imaging, tumor is slightly hyperintense relative to vitreous on T1-weighted images, is dark on T2-weighted images, shows reduced diffusivity on diffusion-weighted images, and demonstrates heterogeneous enhancement with gadolinium. Tumor calcification may be evident as signal voids on susceptibility weighted sequences.

Post laminar optic nerve involvement is a high risk feature (seen in 8% cases) and requires enucleation. Early stages of this are difficult to assess on MRI. Thickening and enhancement of the postlaminar optic nerve on MR imaging usually indicates tumor extension. The most reliable direct MR imaging criteria to rule out advanced optic nerve invasion are normal optic nerve size, normal optic nerve signal on T2-weighted images, and optic nerve enhancement of up to 3 mm on postcontrast imaging.

Intra-arterial chemotherapy is now a standard of care first-line therapy, especially for advanced, unilateral tumors, and carries a lower risk of side effects such as ototoxicity and neurotoxicity associated with systemic chemotherapy.

In cases of heritable retinoblastoma, MRI imaging is also useful in evaluating other concurrent tumours (trilateral / quadrilateral retinoblastoma). Following treatment, MRI is useful for disease surveillance and also long term evaluation for development of additional tumours.


Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy

Rapalino, A. Pourvaziri, M. Maher, A. Jaramillo-Cardoso, B.L. Edlow, J. Conklin, S. Huang, B. Westover, J.M. Romero, E. Halpern, R. Gupta, S. Pomerantz, P. Schaefer, R.G. Gonzalez, S.S. Mukerji, and M.H. Lev

American Journal of Neuroradiology – January 2021

Clinical question:

Characterize the clinical, imaging, and laboratory correlates of COVID-19 leukoencephalopathy.


Observational, retrospective study of consecutive patients admitted to Massachusetts General Hospital between February 1, 2020, and May 12, 2020. Forty-seven consecutive adult patients positive for SARS-CoV-2 who had brain MR imaging were identified. Of these 27 were admitted to the ICU during this study and were included in the analysis.

Findings and results:

Of the 27 patients included in this study, 7 had leukoencephalopathy with reduced diffusivity, 20 did not have leukoencephalopathy with reduced diffusivity. There were no significant racial differences between these groups.

The patients with reduced diffusivity compared with the control group had a significantly higher BMI (p <.01). There were no significant differences in other baseline characteristics such as tobacco use, concurrent illnesses, symptoms before admission, previous cardiac arrest, and number of days symptomatic (including dyspnea).

Patients with reduced diffusivity trended toward more frequent acute renal failure and lower GFRs (p< .06 for both). Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin level (p, .05) and higher serum sodium levels (p. 04) within 24 hours before MR imaging. There were no significant differences between the two groups in rates of septic shock, ischemic bowel, or disseminated intravascular coagulation.

The reduced-diffusivity group showed a reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < 001).


These imaging findings of white matter injury overlaps that of several conditions that may help elucidate the pathophysiology of severe COVID-19 encephalopathy. These include delayed post-hypoxic leukoencephalopathy, sepsis-related leukoencephalopathy, and metabolic encephalopathies related to electrolyte disturbances.


This article furthers our understanding of the possible pathophysiology of imaging finding patterns seen with severe COVID-19 which include borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the cytokine storm associated with the disease.


Radiation-Induced Imaging Changes and Cerebral Edema following Stereotactic Radiosurgery for Brain AVMs

B.J. Daou, G. Palmateer, D.A. Wilkinson, B.G. Thompson, C.O. Maher, N. Chaudhary, J.J. Gemmete, J.A. Hayman, Lam, D.R. Wahl, M. Kim, and A.S. Pandey

American Journal of Neuroradiology – November 2020

Clinical question:

This study aimed to investigate the characteristics and associations of the T2/FLAIR signal response on follow-up MRIs in patients undergoing stereotactic radiosurgery (SRS) for brain AVMs.


The study subjects were obtained following a retrospective review of medical records during a 28 year study period (January 1990 – December 2018). Consecutive patients treated with SRS for brain AVMs who had at least 1 year of follow-up MR imaging were identified. Overall 160 AVMs were treated in 148 patients who were recruited to this study of whom 42 patients were pediatric (26.2%). Logistic regression analysis was used to evaluate predictors of outcomes.

Findings and results:

The median Spetzler-Martin grade was 3. Thirteen AVMs (8.1%) were classified as Martin grade I; 42 (26.3%), as grade II; 71 (44.4%), as grade III; 29 (18.1%), as grade IV; and 5 (3.1%), as grade V. The mean maximal AVM diameter was 2.8 cm. The mean AVM target volume was 7.4 mL, the mean isodose surface volume was 12.5 mL, and the median radiation dose was 16.5 Gy.

New T2/FLAIR signal hyperintensity were noted in 40% of AVMs. T2/FLAIR volumes at 3, 6, 12, 18, and 24 months were, respectively, 4.04, 55.47, 56.42, 48.06, and 29.38 mL.

In patients who developed radiation-induced imaging changes, 45/65 patients (69.2%) had new neurologic signs or symptoms post-SRS. In patients who did not develop imaging changes, 9/95 patients (9.5%) had new neurologic signs or symptoms (p .0001).

122 patients had 2-year imaging follow-up to assess AVM obliteration. In patients who developed radiation-induced imaging changes, 39/46 patients (84.8%) had complete obliteration of their AVMs; in patients who did not develop imaging changes, 55/76 patients (72.4%) had complete AVM obliteration (p .1)

Statistically significant factors associated with radiation induced imaging changes were Spetzler-Martin grade IV, larger maximal diameter, and the presence of multiple feeding arteries.  The occurrence of new neurologic signs and symptoms post-SRS was significantly associated with the presence of radiation induced imaging changes (P<.001).


Radiation-induced imaging changes are common in the post-treatment period following LINAC-based SRS for brain AVMs, peak at about 12 months and are significantly associated with new neurologic signs and symptoms. Patients with larger AVMs and AVMs with multiple feeding arteries have higher odds of developing radiation-induced imaging changes


This study improves our understanding of radiation-induced T2/FLAIR signal abnormality following SRS and its associated factors.


Head CT: Toward Making Full Use of the Information the X-Rays Give

K.A. Cauley, Y. Hu, and S.W. Fielden

American Journal of Neuroradiology – June 2021

In this review, current methods and possible applications of quantitative analysis of head CT imaging is discussed. Godfrey Hounsfield noted that the quantitative capability of CT is one of its major advantages over 2D x-ray, yet the quantitative capabilities of clinical head CT remain largely unexplored.

Although clinical head CT images are typically interpreted qualitatively, automated methods applied to routine clinical head CTs enable quantitative assessment of brain volume, brain parenchymal fraction, brain radiodensity, and brain radiomass.

These metrics gain clinical meaning when viewed relative to a reference database and expressed as quantile regression values. Reference databases can be generated from radiographic studies with normal findings done in patients without significant medical history or without systemic disease. In this way, large databases can be subject to statistical analysis to identify normative parameters.

Quantitative imaging data can aid in objective reporting and in the identification of outliers, with possible diagnostic implications. The comparison to a reference database necessitates standardization of head CT imaging parameters and protocols. Future research is needed to learn the effects of virtual monochromatic imaging on the quantitative characteristics of head CT images.


Variability of Normal Pressure Hydrocephalus Imaging Biomarkers with Respect to Section Plane Angulation: How Wrong a Radiologist Can Be?

Ryska, O. Slezak, A. Eklund, J. Salzer, J. Malm, and J. Zizka

American Journal of Neuroradiology – April 2021

Clinical question:

The aim of this study was to assess the variability of individual iNPH (idiopathic normal pressure hydrocephalus) cross-sectional imaging biomarkers (e.g. Evans Index, callosal angle, simplified callosal angle, frontal horn diameter, etc) with respect to different imaging plane angulations (transverse imaging planes such as the bicallosal, bicommissural, Hypophysis-fastigium [Hy-Fa], and brain stem vertical line).


Eighty subjects (35 with clinically confirmed idiopathic normal pressure hydrocephalus and 45 age- and

sex-matched healthy controls) were prospectively enrolled in a 3T brain MR imaging study. Two independent readers assessed radiologic idiopathic normal pressure hydrocephalus biomarkers on sections aligned parallel or perpendicular to the bicallosal, bicommissural, hypophysis-fastigium, and brain stem vertical lines, respectively.

Findings and results:

Disproportionately enlarged subarachnoid space hydrocephalus, simplified callosal angle, frontal horn diameter, z-Evans Index, and cella media vertical width did not show significant systematic differences in any of 6 section plane combinations studied. The remaining 7 biomarkers (including the Evans Index and callosal angle) showed significant differences in up to 4 of 6 mutually compared section plane combinations. The values obtained from sections aligned with the brain stem vertical line (parallel to the posterior brain stem margin) showed the most deviating results from other section angulations.


Seven of 12 iNPH biomarkers including the frequently used Evans Index and callosal angle showed statistically significant deviations when measured on sections whose angulations differed or did not comply with the proper section definition published in the original literature. Strict adherence to the methodology of iNPH biomarker assessment is, therefore, essential to avoid an incorrect diagnosis. Increased radiologic and clinical attention should be paid to the biomarkers showing low angulation-related variability yet high specificity for iNPH-related morphologic changes such as the z-Evans Index, frontal horn diameter, or disproportionately enlarged subarachnoid space hydrocephalus.


As different institutions use various definitions of transverse and coronal brain imaging sections, comparing imaging sections and biomarkers from different studies may be imprecise as demonstrated in this study on iNPH. This study suggests that systematic effort to standardize and unify cross-sectional imaging plane definitions would bring substantial benefits extending far beyond the radiologic community.

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