Otto Rapalino

Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction.

By application of the MRI method of diffusional kurtosis imaging, a substantially increased diffusional kurtosis was observed within the cerebral ischemic lesions of three stroke subjects, 13–26 h following the onset of symptoms. This increase is interpreted as probably reflecting a higher degree of diffusional heterogeneity in the lesions when compared with normal‐appearing contralateral tissue. In addition, for two of the subjects with white matter infarcts, the increase had a strong fiber tract orientational dependence. It is proposed that this effect is consistent with a large drop in the intra‐axonal diffusivity, possibly related to either axonal varicosities or alterations associated with the endoplasmic reticulum. Copyright

Cranial CT with Adaptive Statistical Iterative Reconstruction: Improved Image Quality with Concomitant Radiation Dose Reduction

Most state-of-the-art CT scanners have some type of iterative reconstruction program that allows for lower patient radiation exposure. At my institution we use it, when available, for most neuroimaging studies. Six levels in 100 CT iterative reconstruction studies were compared with conventional CT obtained previously in the same patients. SNR and CNR were computed and the studies were blindly and qualitatively evaluated. The results showed that iterative reconstruction studies had lower image noise and increased low-contrast resolution while allowing lower radiation doses without affecting spatial resolution. BACKGROUND AND PURPOSE: To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. MATERIALS AND METHODS: Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIR. Phantom data analysis was also performed. RESULTS: Lower-dose scans without ASIR had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%–40%, there was no statistically significant difference in SNR, and at ASIR levels of ≥60%, the SNR values of the reduced-dose scans were significantly higher (P < .01). CNR values were also significantly higher at ASIR levels of ≥40% (P < .01). Blinded qualitative review demonstrated significant improvements in perceived image noise, artifacts, and GM-WM differentiation at ASIR levels ≥60% (P < .01). CONCLUSIONS: These results demonstrate that the use of ASIR in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution.

The pathophysiology of lumbar puncture headache

The pathophysiology of lumbar puncture headache (LPH) is still unclear. There is evidence that leakage of cerebrospinal fluid (CSF) leads to CSF hypotension, which causes dilation of intracranial veins, resulting in LPH. However, CSF leaks at the skull base are not associated with orthostatic headache; there is poor correlation between recumbent CSF pressure and LPH; and there has been no satisfactory explanation of how venous dilation causes orthostatic headache. We propose the hypothesis that LPH is caused by an abnormal distribution of craniospinal elasticity. Increased compliance at the lumbar end of the spinal CSF space, resulting both from anatomic joining of the subarachnoid to the epidural space and from reduced CSF filling pressure, causes the hydrostatic indifferent point to move caudally, creating additional intracranial hypotension and venous dilation in the erect position. We are, thus, able to explain the orthostatic character of LPH, the fact that spinal but not cranial sites of leakage produce orthostatic headache and the imperfect correlations both between recumbent CSF pressure and LPH and between reduced CSF volume and LPH. The near absence of LPH in the very young and in the elderly relates to the relative stiffness of the epidural space at these ages. Epidural injections of blood or saline give immediate relief by reducing epidural distensibility.

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). The biological impact of D-2HG strongly suggests that high levels of this metabolite may play a central role in propagating downstream the effects of mutant IDH, leading to malignant transformation of cells. Hence, D-2HG may be an ideal biomarker for both diagnosing and monitoring treatment response targeting IDH mutations. Magnetic resonance spectroscopy (MRS) is well suited to the task of noninvasive D-2HG detection, and there has been much interest in developing such methods. Here, we review recent efforts to translate methodology using MRS to reliably measure in vivo D-2HG into clinical research.

Accuracy of the Alberta Stroke Program Early CT Score during the First 3 Hours of Middle Cerebral Artery Stroke: Comparison of Noncontrast CT, CT Angiography Source Images, and CT Perfusion

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a reliable method of delineating the extent of middle cerebral artery (MCA) stroke. Our aim was to retrospectively compare the accuracy of ASPECTS on noncontrast CT, CT angiography (CTA) source images, and CT perfusion maps of cerebral blood volume (CBV) during the first 3 hours of middle cerebral artery (MCA) stroke. MATERIALS AND METHODS: First-time patients with MCA stroke who presented <3 hours from symptom onset and were evaluated by noncontrast CT/CTA/CT perfusion, had confirmed acute nonlacunar MCA infarct on diffusion-weighted MR imaging (DWI) within 7 days, and had follow-up angiography were included. Patients were excluded for persistent MCA occlusion or stenosis. Two raters through consensus assigned an ASPECTS on the noncontrast CT, CTA source images, and the section-selective (2 × 12 mm coverage) CT perfusion CBV maps. ASPECTS on follow-up DWI served as the reference standard. For each CT technique, the detection rates of regional infarction, the mean ASPECTS, and the linear correlation to final ASPECTS were determined and compared. P values <.05 were considered significant. RESULTS: Twenty-eight patients satisfied the criteria with DWI performed at a mean of 50.3 hours (range, 22–125 hours) post-CT imaging. Of 280 ASPECTS regions, 100 were infarcted on DWI. The accuracy of noncontrast CT, CTA source images, and CT perfusion CBV for detecting regional infarct was 80.0%, 84.3%, and 96.8%, respectively (P < .0001). The mean ASPECTSs of noncontrast CT, CTA source images, CT perfusion CBV, and DWI were 8.4 ± 1.8, 8.0 ± 1.8, 6.8 ± 1.9, and 6.5 ± 1.8, respectively. The mean noncontrast CT and CTA source image ASPECTS was different from that of DWI (P < .05). Correlation of noncontrast CT, CTA source images, and CT perfusion CBV ASPECTS with final ASPECTS was r2 = 0.34, r2 = 0.42, and r2 = 0.91, respectively. CONCLUSION: In a retrospective cohort of MCA infarcts imaged <3 hours from stroke onset, ASPECTS was most accurately determined on CT perfusion CBV maps.

Virtual Monochromatic Reconstruction of Dual-Energy Unenhanced Head CT at 65–75 keV Maximizes Image Quality Compared with Conventional Polychromatic CT

PURPOSE To determine the virtual monochromatic imaging (VMI) energy levels that maximize brain parenchymal image quality in dual-energy unenhanced head computed tomography (CT) and to assess the improvement with this technique compared with conventional polychromatic scanning. MATERIALS AND METHODS Institutional review board approval was obtained with no informed consent required for this HIPAA-compliant retrospective analysis. Twenty-five consecutive unenhanced head CT scans were acquired with a 64-section dual-energy scanner with fast tube voltage switching (80-140 kVp). Scans were retrospectively reconstructed at VMI energy levels from 40 to 140 keV in 5-keV increments and were analyzed by using four quality indexes: gray matter (GM) signal-to-noise ratio (SNR), white matter (WM) SNR, GM-WM contrast-to-noise ratio (CNR), and posterior fossa artifact index (PFAI). Optimal mean values for each parameter were compared with those from 50 consecutive scans obtained with the same scanner in 120-kVp single-energy mode. Repeated-measures analysis of variance and Dunnett post hoc t test were then used to determine significance. RESULTS Maximal GM SNR, WM SNR, and GM-WM CNR values were observed at 65 keV, and minimal PFAI was observed at 75 keV. These values were significantly better than those of conventional polychromatic CT (P < .01); quality index improvement ratios (corrected for radiation dose) ranged from 17% to 50%. CONCLUSION Virtual monochromatic reconstruction of dual-energy unenhanced head CT scans at 65-75 keV (optimal energy levels) maximizes image quality compared with scans obtained with conventional polychromatic CT.

The Massachusetts General Hospital acute stroke imaging algorithm: an experience and evidence based approach

The Massachusetts General Hospital Neuroradiology Division employed an experience and evidence based approach to develop a neuroimaging algorithm to best select patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs) for intravenous tissue plasminogen activator and endovascular treatment. Methods found to be of value included the National Institutes of Health Stroke Scale (NIHSS), non-contrast CT, CT angiography (CTA) and diffusion MRI. Perfusion imaging by CT and MRI were found to be unnecessary for safe and effective triage of patients with severe ACOs. An algorithm was adopted that includes: non-contrast CT to identify hemorrhage and large hypodensity followed by CTA to identify the ACO; diffusion MRI to estimate the core infarct; and NIHSS in conjunction with diffusion data to estimate the clinical penumbra.

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

PURPOSE The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. METHODS AND MATERIALS Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. RESULTS A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. CONCLUSIONS The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury

BACKGROUND Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. METHODS AND MATERIALS We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. RESULTS At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). CONCLUSIONS Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Slice accelerated gradient-echo spin-echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage

To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous‐multiple‐slice (SMS) method.