Validation of daily 0.35 T diffusion-weighted MRI for MRI-guided glioblastoma radiotherapy.

BACKGROUND: MRI-Linac systems enable daily diffusion-weighed imaging (DWI) MRI scans for assessing glioblastoma tumor changes with radiotherapy treatment. PURPOSE: Our study assessed the image quality of echoplanar imaging (EPI)-DWI scans compared with turbo spin echo (TSE)-DWI scans at 0.35 Tesla (T) and compared the apparent diffusion coefficient (ADC) values and distortion of EPI-DWI on 0.35 T MRI-Linac compared to high-field diagnostic MRI scanners. METHODS: The calibrated National Institute of Standards and Technology (NIST)/Quantitative Imaging Biomarkers Alliance (QIBA) Diffusion Phantom was scanned on a 0.35 T MRI-Linac, and 1.5 T and 3 T MRI with EPI-DWI. Five patients were scanned on a 0.35 T MRI-Linac with a TSE-DWI sequence, and five other patients were scanned with EPI-DWI on a 0.35 T MRI-Linac and a 3 T MRI. The quality of images was compared between the TSE-DWI and EPI-DWI on the 0.35 T MRI-Linac assessing signal-to-noise ratios and presence of artifacts. EPI-DWI ADC values and distortion magnitude were measured and compared between 0.35 T MRI-Linac and high-field MRI for both phantom and patient studies. RESULTS: The average ADC differences between EPI-DWI acquired on the 0.35 T MRI-Linac, 1.5 T and 3 T MRI scanners and published references in the phantom study were 1.7%, 0.4% and 1.0%, respectively. Comparing the ADC values based on EPI-DWI in glioblastoma tumors, there was a 3.36% difference between 0.35 and 3 T measurements. Susceptibility-induced distortions in the EPI-DWI phantoms were 0.46 ± 1.51 mm for 0.35 MRI-Linac, 0.98 ± 0.51 mm for 1.5 T MRI and 1.14 ± 1.88 mm for 3 T MRI; for patients -0.47 ± 0.78 mm for 0.35 T and 1.73 ± 2.11 mm for 3 T MRIs. The mean deformable registration distortion for a phantom was 1.1 ± 0.22 mm, 3.5 ± 0.39 mm and 4.7 ± 0.37 mm for the 0.35 T MRI-Linac, 1.5 T MRI, and 3 T MRI scanners, respectively; for patients this distortion was -0.46 ± 0.57 mm for 0.35 T and 4.2 ± 0.41 mm for 3 T. EPI-DWI 0.35 T MRI-Linac images showed higher SNR and lack of artifacts compared with TSE-DWI, especially at higher b-values up to 1000 s/mm2. CONCLUSION: EPI-DWI on a 0.35 T MRI-Linac showed superior image quality compared with TSE-DWI, minor and less distortions than high-field diagnostic scanners, and comparable ADC values in phantoms and glioblastoma tumors. EPI-DWI should be investigated on the 0.35 T MRI-Linac for prediction of early response in patients with glioblastoma.

A Deep Learning Approach for Automatic Segmentation during Daily MRI-Linac Radiotherapy of Glioblastoma.

Glioblastoma changes during chemoradiotherapy are inferred from high-field MRI before and after treatment but are rarely investigated during radiotherapy. The purpose of this study was to develop a deep learning network to automatically segment glioblastoma tumors on daily treatment set-up scans from the first glioblastoma patients treated on MRI-linac. Glioblastoma patients were prospectively imaged daily during chemoradiotherapy on 0.35T MRI-linac. Tumor and edema (tumor lesion) and resection cavity kinetics throughout the treatment were manually segmented on these daily MRI. Utilizing a convolutional neural network, an automatic segmentation deep learning network was built. A nine-fold cross-validation schema was used to train the network using 80:10:10 for training, validation, and testing. Thirty-six glioblastoma patients were imaged pre-treatment and 30 times during radiotherapy (n = 31 volumes, total of 930 MRIs). The average tumor lesion and resection cavity volumes were 94.56 ± 64.68 cc and 72.44 ± 35.08 cc, respectively. The average Dice similarity coefficient between manual and auto-segmentation for tumor lesion and resection cavity across all patients was 0.67 and 0.84, respectively. This is the first brain lesion segmentation network developed for MRI-linac. The network performed comparably to the only other published network for auto-segmentation of post-operative glioblastoma lesions. Segmented volumes can be utilized for adaptive radiotherapy and propagated across multiple MRI contrasts to create a prognostic model for glioblastoma based on multiparametric MRI.

Simulated Adaptive Radiotherapy for Shrinking Glioblastoma Resection Cavities on a Hybrid MRI-Linear Accelerator.

During radiation therapy (RT) of glioblastoma, daily MRI with combination MRI-linear accelerator (MRI-Linac) systems has demonstrated significant anatomic changes, including evolving post-surgical cavity shrinkage. Cognitive function RT for brain tumors is correlated with radiation doses to healthy brain structures, especially the hippocampi. Therefore, this study investigates whether adaptive planning to the shrinking target could reduce normal brain RT dose with the goal of improving post-RT function. We evaluated 10 glioblastoma patients previously treated on a 0.35T MRI-Linac with a prescription of 60 Gy delivered in 30 fractions over six weeks without adaptation ("static plan") with concurrent temozolomide chemotherapy. Six weekly plans were created per patient. Reductions in the radiation dose to uninvolved hippocampi (maximum and mean) and brain (mean) were observed for weekly adaptive plans. The dose (Gy) to the hippocampi for static vs. weekly adaptive plans were, respectively: max 21 ± 13.7 vs. 15.2 ± 8.2 (p = 0.003) and mean 12.5 ± 6.7 vs. 8.4 ± 4.0 (p = 0.036). The mean brain dose was 20.6 ± 6.0 for static planning vs. 18.7 ± 6.8 for weekly adaptive planning (p = 0.005). Weekly adaptive re-planning has the potential to spare the brain and hippocampi from high-dose radiation, possibly reducing the neurocognitive side effects of RT for eligible patients.

Internal Carotid Artery Angle Variations are Poorly Explained by Vascular Risk Factors: The Northern Manhattan Study.

OBJECTIVES: The internal carotid artery (ICA) angle of origin may contribute to atherogenesis by altered hemodynamics. We aim to determine the contribution of vascular risk factors and arterial wall changes to ICA angle variations. METHODS: We analyzed 1,065 stroke-free participants from the population-based Northern Manhattan Study who underwent B-mode ultrasound (mean age 68.7±8.9 years; 59% women). ICA angle was estimated at the intersection between the common carotid artery and the ICA center line projections. Narrower external angles translating into greater carotid bifurcation bending were considered unfavorable. Linear regression models were fitted to assess the relationship between ICA angle and demographics, vascular risk factors, and arterial wall changes including carotid intima-media thickness (cIMT) and plaque presence. RESULTS: ICA angles were narrower on the left compared to the right side (153±15.4 degrees versus 161.4±12.7 degrees, p<0.01). Mean cIMT was 0.9±0.1 mm and 54.3% had at least one plaque. ICA angle was not associated with cIMT or plaque presence. Unfavorable left and right ICA angles were associated with advanced age (per 10-year increase ß=-1.6; p=0.01, and -1.3; p=0.03, respectively) and being Black participant (ß=-4.6; p<0.01 and -2.9; p=0.04, respectively), while unfavorable left ICA angle was associated with being female (ß=-2.8; p=0.03) and increased diastolic blood pressure (per 10 mmHg increase ß=-2.1; p<0.01). Overall, studied factors explained less than 10% of the variance in ICA angle (left R2=0.07; right R2=0.05). CONCLUSION: Only a small portion of ICA angle variation were explained by demographics, vascular risk factors and arterial wall changes. Whether ICA angle is determined by other environmental or genetic factors, and is an independent risk factor for atherogenesis, requires further investigation.

Rapid Apparent Diffusion Coefficient Evolution After Early Revascularization.

Background and Purpose- In this era of endovascular therapy (EVT) with early, complete recanalization and reperfusion, we have observed an even more rapid apparent diffusion coefficient (ADC) normalization within the acute ischemic lesion compared with the natural history or IV-tPA-treated patient. In this study, we aimed to evaluate the effect of revascularization on ADC evolution within the core lesion in the first 24 hours in acute ischemic stroke patients. Methods- This retrospective study included anterior circulation acute ischemic stroke patients treated with EVT with or without intravenous tPA (IVT) from 2015 to 2017 compared with a consecutive cohort of IVT-only patients treated before 2015. Diffusion-weighted imaging and ADC maps were used to quantify baseline core lesions. Median ADC value change and core reversal were determined at 24 hours. Diffusion-weighted imaging lesion growth was measured at 24 hours and 5 days. Good clinical outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Results- Twenty-five patients (50%) received IVT while the other 25 patients received EVT (50%) with or without IVT. Between these patient groups, there were no differences in age, sex, baseline National Institutes of Health Stroke Scale, interhospital transfer, or IVT rates. Thirty-two patients (64%) revascularized with 69% receiving EVT. There was a significant increase in median ADC value of the core lesion at 24 hours in patients who revascularized compared with further ADC reduction in nonrevascularization patients. Revascularization patients had a significantly higher rate of good clinical outcome at 90 days, 63% versus 9% (P=0.003). Core reversal at 24 hours was significantly higher in revascularization patients, 69% versus 22% (P=0.002). Conclusions- ADC evolution in acute ischemic stroke patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding. The early ADC normalization we have observed in this setting may include a component of secondary injury and serve as a potential imaging biomarker for the development of future adjunctive therapies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients.

Background and Purpose- The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization. Methods- Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0-2 using the latest available modified Rankin Scale score. Results- Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%; P=0.001), any hemorrhagic transformation (60% versus 36%; P=0.04) and poor clinical outcome (67% versus 36%; P=0.008). Only age (odds ratio, 1.1; 95% CI, 1.01-1.12; P=0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93-26.92; P=0.003). Conclusions- In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Recurrent thrombolysis of a stuttering lacunar infarction captured on serial MRIs.

Lacunar strokes account for about a fourth of all ischemic strokes. Pontine infarcts often present with stuttering symptoms, referred to as pontine warning syndrome (PWS). Patients presenting with fluctuating symptoms can appear to have rapidly improving symptoms and thus often go untreated despite the risk of recurrent deficits. MRI carries a higher sensitivity in detecting posterior circulation strokes compared to computed topagraphy, but does not always indicate irreversible injury. Here we present the first description of a stuttering lacune, captured radiographically on serial magnetic resonance imaging (MRI), that was initially averted with the administration of intravenous (IV) tissue plasminogen activator (tPA), only to return a month later and progress on imaging despite re-administration of tPA. During the first admission, our patient had spontaneous resolution of symptoms with complete reversal on restricted diffusion soon after IV tPA administration. On the second admission, the stuttering symptoms returned as did the same pontine lesion. Although his stuttering lesions lasted for several days, and the pontine lesion did ultimately progress to partial infarction on MRI, he was discharged home without neurologic deficits. Our case suggests that tPA may be of benefit in patients with lacunar pontine strokes even if symptoms rapidly improve or resolve.