Final Lesion Volume Research Articles

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes.

Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed. Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice. These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

Abstract TP306: Anemia Causes Hematoma Expansion, Cerebral Hypoxia-Driven Microglial Activation, and Early Mortality in Mice With Intracerebral Hemorrhage

Anemic intracerebral hemorrhage (ICH) patients are observed to have poor clinical outcomes with increased risk of hematoma expansion (HE) and impaired cerebral oxygenation. To assess whether anemia causes these observations, we assessed neuroimaging evidence of HE and neuropathological changes of hypoxia and blood brain barrier (BBB) dysfunction in anemic vs non-anemic mice with ICH. Anemia was generated in 3 month old female C57/BL6 mice using iron-deficient chow. Age and sex-matched controls were fed iron-replete control diet. Anemia was verified using modified Drabkin assays. Collagenase was used to induce ICH. ICH volume and HE were quantified using serial T2-weighed MRI at 1, 4, and 24 hours after ICH. Early 24 hour mortality was recorded. After the last MRI, surviving mice were euthanized by intracardiac perfusion and the brain was processed for histological analysis of vascular permeability (IgG), microglia number and activation (Iba1 and CD68), and response to hypoxia (HIF1α). Statistical analyses were performed using two-tailed ANOVA. Compared to controls, anemic mice displayed larger final ICH lesion volumes (anemia: 7.7 mm 3 vs control: 6.1 mm 3 ), greater HE at 24 hours (anemia: 111.4% vs control: 23.6%) and increased early mortality (anemia: 30% vs control: 0%). Histological analyses revealed that, while microglial activation and BBB permeability to serum IgGs in control mice were restricted to the ipsilateral hemisphere and mostly localized perilesionally, anemic mice had increased immune infiltration and increased BBB permeability in both hemispheres. Similarly, non-ICH anemic mice showed increased and widespread immune cell infiltration and increased BBB permeability compared to non-ICH control mice, suggesting that consistently low hemoglobin concentrations may increase cerebrovascular susceptibility to injury.Future studies will be needed to further clarify cellular and molecular mechanisms driving our findings and whether anemia can be a treatable target to improve ICH outcomes.

Blood-Brain Barrier Permeability and Kinetics of Inflammatory Markers in Acute Stroke Patients Treated With Thrombectomy.

The aim of this study was to investigate the relationship between baseline blood-brain barrier (BBB) permeability and the kinetics of circulating inflammatory markers in a cohort of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. The CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke includes AIS patients treated with mechanical thrombectomy after admission MRI and undergoing a sequential assessment of circulating inflammatory markers. Baseline dynamic susceptibility perfusion MRI was postprocessed with arrival time correction to provide K2 maps reflecting BBB permeability. After coregistration of apparent diffusion coefficient and K2 maps, the 90th percentile of K2 value was extracted within baseline ischemic core and expressed as a percentage change compared with contralateral normal-appearing white matter. Population was dichotomized according to the median K2 value. Univariable and multiple variable logistic regression analyses were performed to investigate factors associated with increased pretreatment BBB permeability in the whole population and in patients with symptom onset <6 hours. In the whole population (n = 105 patients, median K2 = 1.59), patients with an increased BBB permeability had higher serum levels of matrix metalloproteinase (MMP)-9 at H48 (p = 0.02), a higher C-reactive protein (CRP) serum level at H48 (p = 0.01), poorer collateral status (p = 0.01), and a larger baseline ischemic core (p < 0.001). They were more likely to have hemorrhagic transformation (p = 0.008), larger final lesion volume (p = 0.02), and worst neurologic outcome at 3 months (p = 0.04). The multiple variable logistic regression indicated that an increased BBB permeability was associated only with ischemic core volume (odds ratio [OR] 1.04, 95% CI 1.01-1.06, p < 0.0001). Restricting analysis to patients with symptom onset <6 hours (n = 72, median K2 = 1.27), participants with an increased BBB permeability had higher serum levels of MMP-9 at H0 (p = 0.005), H6 (p = 0.004), H24 (p = 0.02), and H48 (p = 0.01), higher CRP levels at H48 (p = 0.02), and a larger baseline ischemic core (p < 0.0001). The multiple variable logistic analysis showed that increased BBB permeability was independently associated with higher H0 MMP-9 levels (OR 1.33, 95% CI 1.12-1.65, p = 0.01) and a larger ischemic core (OR 1.27, 95% CI 1.08-1.59, p = 0.04). In AIS patients, increased BBB permeability is associated with a larger ischemic core. In the subgroup of patients with symptom onset <6 hours, increased BBB permeability is independently associated with higher H0 MMP-9 levels and a larger ischemic core.

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Prediction of Tissue Damage Using a User-Independent Machine Learning Algorithm vs. Tmax Threshold Maps

(1) Background: To test the accuracy of a fully automated stroke tissue estimation algorithm (FASTER) to predict final lesion volumes in an independent dataset in patients with acute stroke; (2) Methods: Tissue-at-risk prediction was performed in 31 stroke patients presenting with a proximal middle cerebral artery occlusion. FDA-cleared perfusion software using the AHA recommendation for the Tmax threshold delay was tested against a prediction algorithm trained on an independent perfusion software using artificial intelligence (FASTER). Following our endovascular strategy to consequently achieve TICI 3 outcome, we compared patients with complete reperfusion (TICI 3) vs. no reperfusion (TICI 0) after mechanical thrombectomy. Final infarct volume was determined on a routine follow-up MRI or CT at 90 days after the stroke; (3) Results: Compared to the reference standard (infarct volume after 90 days), the decision forest algorithm overestimated the final infarct volume in patients without reperfusion. Underestimation was observed if patients were completely reperfused. In cases where the FDA-cleared segmentation was not interpretable due to improper definitions of the arterial input function, the decision forest provided reliable results; (4) Conclusions: The prediction accuracy of automated tissue estimation depends on (i) success of reperfusion, (ii) infarct size, and (iii) software-related factors introduced by the training sample. A principal advantage of machine learning algorithms is their improved robustness to artifacts in comparison to solely threshold-based model-dependent software. Validation on independent datasets remains a crucial condition for clinical implementations of decision support systems in stroke imaging.

Impact of Time Interval Between Diagnostic and Planning MRI on Tumor Volume and Anatomic Displacement for Brain Metastases Undergoing Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is increasingly used in brain metastasis patients. However, the impact of the timing on tumor volume change and tumor anatomical displacement between the diagnostic and treatment planning imaging is not well studied.Consecutive patients diagnosed with brain metastases and treated with SRS between July, 2017 and June, 2020 were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) with identical imaging parameters were included. The impact of histology, inter-scan interval, lesion location, volume and size were evaluated on final lesion size, volume and anatomic displacement. Correlations were assessed using Kendall's rank correlation. The Kruskal Wallis rank sum test was used for all other comparisons.We included 101 eligible patients (531 lesions) with median inter-scan interval of 8 days (range: 1-42); 50% were NSCLC and 25% breast cancer. The three most common locations of lesions were the frontal (181 lesions, 34%), temporal (96, 18%), cerebellar (91, 17%) lobes. Median MRI-1 diameter and volume were 0.50 cm (Range: 0.23-0.89 cm) and 0.06 cm3 (Range: 0.01-4.62 cm3), respectively. Median percentage change in lesion diameter and volume were +9.5% (Range: -8.4% to +61.2%) and +20% (Range: -20% to +200%), respectively. Overall, there was a statistically significant change in percent tumor volume change between MRI-1 to MRI-2 (P = 0.01). Directional displacements exceeded 1 mm in 18 (3%) lesions in right to left (RL), 28 (5%) superior to inferior (SI), and 25 (4.7%) anterior to posterior (AP) directions. Overall, 355 (67%) lesions had any displacement in at least 1 direction between MRI-1 and MRI-2 and 205 (38%) in all 3 directions. Median lesion centroid displacement was 0.48 mm (0.10-3.09 mm) and was larger than 1 mm in 66 (12%) lesions. Differences were also observed across tumor histologies (P = 0.01); melanoma brain metastases had the largest magnitude changes. Tumor displacement also differed across various histologies with largest displacement in renal cell carcinoma metastases (P < 0.001). Magnitude of displacement was also significantly associated with tumor location (P = 0.03) with the largest displacement in parietal lobe lesions. Across all lesions, there was a difference in tumor size change in patients treated on corticosteroids (P = 0.01).Volumetric and positional changes can occur during the planning process for SRS and are histology and location specific. Additional analyses are key to understanding the impact of each of these variables, corticosteroids, and systemic therapy to better understand and model tumor dynamics.T. Kutuk: None. R.P. Tolakanahalli: None. A. Williams: None. M.C. Tom: Research Grant; Blue Earth Diagnostics. J.D. Vadhan: None. H. Appel: None. M.D. Hall: Research Grant; Florida Department of Health; Proton Collaborative Group (PCG) Executive Council. D. Wieczorek: None. S.D. Davis: None. M.W. McDermott: Consultant; Stryker, Diende. V. Siomin: None. M.D. Chuong: Research Grant; ViewRay, AstraZeneca. Honoraria; ViewRay, Sirtex, Accuray. Speaker's Bureau; ViewRay, Sirtex, Accuray. Advisory Board; ViewRay, Advanced Accelerator Applications. Travel Expenses; ViewRay, AstraZeneca, Accuray; Particle Therapy Cooperative Group. Manages the operations and activities within the proton center; Miami Cancer. M.P. Mehta: None. A. Gutierrez: Honoraria; ViewRay, Elekta. R. Kotecha: None.

Automated Final Lesion Segmentation in Posterior Circulation Acute Ischemic Stroke Using Deep Learning.

Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83–0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41–77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.

Impact of MRI timing on tumor volume and anatomic displacement for brain metastases undergoing stereotactic radiosurgery.

The objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM). Consecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning). 101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001). Changes in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.

Ischemic lesion volume prediction in thrombolysis treated wake-up stroke patients

There is growing research interest on identification of CT Perfusion (CTP) parameters that predict the outcome in acute ischemic stroke patients. The aim of this study is to produce the model, based on core-penumbra related parameters assessed by CTP processing and commonly used clinical prediction factors, to predict the final infarct volume in thrombolysis-treated anterior circulation wake-up stroke (WUS) patients. The study was conducted on 51 consecutive wake-up ischemic stroke patients. The model for the predictive estimation of final ischemic volume was determined by using the Least Absolute Shrinkage and Selection Operator (LASSO) regularized least-squares regression. The results showed that CTP core volume and CTP total ischemic volume at admission, together with ASPECT score predict the final infarct lesion volume. In particular, the identified model presented 5-fold cross-validation root mean square error RMSE of 8.1 ml and the coefficient of determination (R2=0.94) on our dataset. The results should be confirmed in a lager study. In conclusion, in this study we preliminarily identified a predictive model to estimate final ischemic lesion volume in thrombolysis treated wake-up stroke patients.

A cohort study of microwave ablation and surgery for low-risk papillary thyroid microcarcinoma

Background The optimal treatment method for papillary thyroid microcarcinoma (PTMC) is lacking consensus. Here we aimed to compare the efficacy and safety of surgery and microwave ablation (MWA) for PTMC. Methods The clinical data of 644 patients with PTMC treated between July 2013 and June 2020 were retrospectively analyzed. A total of 320 and 324 patients underwent MWA and surgery, respectively. We observed lesion changes in the MWA group and compared the recurrence, metastasis, complications, and other health economic indicators between the 2 groups. Results The mean follow-up time was 890.7 ± 532.9 (187.9–2679.0) days in the MWA group and 910.9 ± 568.4 (193.8–2821.5) days in the surgery group. In the MWA group, lesion volume increased significantly after ablation and then gradually decreased. The final lesion volume reduction rate was 90.73% ± 7.94%, and 193 lesions (60.3%) disappeared completely. There were no significant intergroup differences in recurrence or metastasis. The incidence of main complications (temporary hypothyroidism, hypoparathyroidism, and temporary hoarseness) was significantly lower in the MWA group than in the surgery group (p < 0.001). The treatment time, intraoperative blood loss, and hospital stay were significantly lower in the MWA group than in the surgery group (p < 0.001). Conclusions MWA is effective for treating PTMC, with a low incidence of complications and less trauma. The rates of post-treatment recurrence and metastasis are similar to those of surgery, indicating that MWA is a suitable alternative to surgery.

Abstract WP83: Validation of a Relative Non-Contrast CT Map to Detect Early Ischemic Changes in Acute Stroke

Background: Discerning signs of early infarct on the non-contrast CT (NCCT) can be difficult. To facilitate interpretation of the NCCT we previously developed a technique to generate symmetry ratio maps of the NCCT (rNCCT maps) on which subtle (≥5%) differences in density between symmetric brain regions are enhanced. We sought to validate the rNCCT map against other measures of early infarction in a large cohort. Methods: rNCCT maps were generated for 146 ischemic stroke patients. We assessed how often a neurologist’s interpretation of the NCCT was changed when provided with the rNCCT map. The neurologist was blinded to CTP and DWI but was given the infarct hemisphere. In addition, using the 24-hour DWI as the gold standard, we assessed the sensitivity, specificity and volumetric accuracy of the rNCCT-defined infarct core and compared this to the test characteristics of CTP-defined infarct core (CBF&lt;38% threshold). Results: Addition of rNCCT overlay map changed clinician’s initial read 64.4% of the time (95% CI 56-72%); the rNCCT identified new areas of ischemia not appreciated on blinded review 86.2% of the time (95% CI 78-92%) and in 35.1% helped rule out early ischemia where the reader was unsure of its presence (95% CI 26-45%). In the 53 patients with reperfusion and follow-up MRI, specificity of rNCCT for final lesion volume was 99.5% for rNCCT [98.5-99.8%] vs. 99.8% [IQR 98.8-99.9%] for CTP (P=0.08). Sensitivity for rNCCT was 19.9% [7.1-28.1%] vs. 17.5% [4.7-32.2%] for CTP (P=0.56). Conclusions: This study validates the rNCCT map for detection of early ischemic changes. It is more quantitative and objective than a clinician’s read of the NCCT alone. The sensitivity and specificity for detecting early ischemic changes on rNCCT were comparable to those achieved with CTP. This indicates that the rNCCT could be a valuable tool in the evaluation of acute stroke patients.

Individualized quantification of the benefit from reperfusion therapy using stroke predictive models.

Recent imaging developments have shown the potential of voxel-based models in assessing infarct growth after stroke. Many models have been proposed but their relevance in predicting the benefit of a reperfusion therapy remains unclear. We searched for a predictive model whose volumetric predictions would identify stroke patients who are to benefit from tissue plasminogen activator (t-PA)-induced reperfusion. Forty-five cases were used to study retrospectively stroke progression from admission to end of follow-up. Predictive approaches based on various statistical models, predictive variables and spatial filtering methods were compared. The optimal approach was chosen according to the area under the precision-recall curve (AUPRC). The final lesion volume was then predicted assuming that the patient would or would not reperfuse. Patients, with an acute lesion of ≤50ml and a predicted reduction in the presence of reperfusion >6ml and >25% of the acute lesion, were classified as responders. The optimal model was a logistic regression using the voxel distance to the acute lesion, the volume of the acute lesion and Gaussian-filtered MRI contrast parameters as predictive variables. The predictions gave a median AUPRC of 0.655, a median AUC of 0.976 and a median volumetric error of 8.29ml. Nineteen patients matched the responder profile. A non-significant trend of improved reduction in NIHSS score (-42.8%, p=.09) and in lesion volume (-78.1%, p=0.21) following reperfusion was observed for responder patients. Despite limited volumetric accuracy, predictive stroke models can be used to quantify the benefit of reperfusion therapies.

Impact of Collateral Status on Neuroprotective Effect of Cyclosporine A in Acute Ischemic Stroke

Neuroprotection for acute ischemic stroke remains an elusive goal. Intracranial collaterals may favor neuroprotective drugs delivery at the acute stage of ischemic stroke. A recent phase 2 study showed that cyclosporine A (CsA) reduced ischemic damage in patients with a proximal occlusion who experienced effective recanalization. Collateral flow may improve this benefit. Collateral supply was assessed using dynamic susceptibility contrast MRI in 47 patients among the 110 patients from the original study and were graded in two groups: good collaterals and poor collaterals. Patients with good collaterals had significantly smaller initial infarct in both CsA group (p = 0.003) and controls (p = 0.016). Similarly, the final lesion volume was significantly lower in patients with good collaterals in both groups. In patients with either good or poor collaterals CsA showed no additional benefit on ischemic lesion progression and final infarct size at day 30. We failed to demonstrate any significant additional benefit of CsA in patients with good collateral circulation.

Collateral circulation assessment within the 4.5 h time window in patients with and without DWI/FLAIR MRI mismatch

ObjectivesThe aim of the present study was to assess the association between collateral status and DWI-FLAIR mismatch in patients with acute ischemic stroke within the 4.5 h time-window. MethodsWe analysed DWI, FLAIR, and PWI data in patients within 4.5 h after symptom onset from the I-KNOW European database. Collateral flow maps were graded by analyzing contrast ‘staining’ extent over the early, mid and late perfusion phases. ADC values, DWI lesion volume, and normalised perfusion parameters (CBV,Tmax) within DWI lesions were determined. Visibility of parenchymal hyperintensivty on FLAIR was evaluated (“FLAIR positive”), and DWI-FLAIR mismatch was assessed. Spontaneously reperfused regions were defined as voxels with Tmax <6 s within the DWI lesion. Final infarct size was assessed on day-30 FLAIR images. ResultsOf the 168 patients included in I-KNOW database, 87 were eligible for this study. DWI-FLAIR mismatch was present in 69 patients. There was no difference between poor and good collaterals status according to age, sex, baseline NIHSS score, time to MRI and DWI lesion volume. Collateral status was significantly better in the FLAIR positive group (p = .001). Patients with poor collaterals had significantly increased Tmax (p = .005). Baseline DWI lesion volume and final lesion volume were significantly smaller in patients with good collateral status (p < .001 and 0.01, respectively). ConclusionsWe found that patients with early FLAIR lesion visibility have a better collateral status. This finding has implications for the management of stroke patients with unknown time-of-onset, and more widely should be considered in the current context of extending the therapeutic window.

Subacute Infarct Volume With Edema Correction in Computed Tomography Is Equivalent to Final Infarct Volume After Ischemic Stroke: Improving the Comparability of Infarct Imaging Endpoints in Clinical Trials.

Final infarct volume is regularly used as an end point of tissue outcome in stroke trials; however, the reported volumes are most commonly derived from early follow-up imaging. Those volumes are significantly impaired by ischemic edema, which causes an overestimation of the true final lesion volume. As net water uptake within ischemic brain can be quantified densitometrically in computed tomography (CT) as recently described, we hypothesized that the final lesion volume can be better estimated by correcting the lesion volume in early follow-up for the corresponding proportion of edema. After retrospective consecutive screening of the local registry, 20 patients with acute middle cerebral artery large vessel occlusion met the inclusion criteria with early and late follow-up CT; the latter acquired at least 4 weeks after admission. In early follow-up imaging 24 hours after onset, the proportion of edema contributing to the infarct lesion was calculated by quantifying the total volume of ischemic net water uptake. Edema volume was then subtracted from the total lesion volume to obtain edema-corrected lesion volumes. Finally, these corrected lesion volumes were compared with the final lesion volume on late follow-up serving as ground truth. The median lesion volume in the early follow-up was 115.1 mL (range, 21.9-539.9 mL) and significantly exceeded the median final lesion volume in the late follow-up CT, which was 86.6 mL (range, 11.2-399.0 mL; p < 0.001). The calculated mean proportion of edema within the early lesion volume was 25.8% (±5.9%; range, 11.1%-35.9%. The median edema-corrected lesion volume measured after 24 hours was 87.1 mL (range, 18.2-376.3 mL). The estimation of final lesion volume in the early follow-up CT was therefore improved by a mean of 31.4% (±2.1%) when correcting for the proportion of edema and did not differ significantly from the true final infarct volume (p = 0.2). Edema-corrected volumes of early follow-up infarct lesion in CT were in close agreement with the actual final infarct volumes. Computed tomography-based edema correction of subacute infarct lesions improves the estimation of final tissue outcome. This could especially improve the comparability of imaging end points and facilitate patient recruitment in clinical trials.

Prediction of Tissue Outcome and Assessment of Treatment Effect in Acute Ischemic Stroke Using Deep Learning.

Treatment options for patients with acute ischemic stroke depend on the volume of salvageable tissue. This volume assessment is currently based on fixed thresholds and single imagine modalities, limiting accuracy. We wish to develop and validate a predictive model capable of automatically identifying and combining acute imaging features to accurately predict final lesion volume. Using acute magnetic resonance imaging, we developed and trained a deep convolutional neural network (CNNdeep) to predict final imaging outcome. A total of 222 patients were included, of which 187 were treated with rtPA (recombinant tissue-type plasminogen activator). The performance of CNNdeep was compared with a shallow CNN based on the perfusion-weighted imaging biomarker Tmax (CNNTmax), a shallow CNN based on a combination of 9 different biomarkers (CNNshallow), a generalized linear model, and thresholding of the diffusion-weighted imaging biomarker apparent diffusion coefficient (ADC) at 600×10-6 mm2/s (ADCthres). To assess whether CNNdeep is capable of differentiating outcomes of ±intravenous rtPA, patients not receiving intravenous rtPA were included to train CNNdeep,-rtpa to access a treatment effect. The networks' performances were evaluated using visual inspection, area under the receiver operating characteristic curve (AUC), and contrast. CNNdeep yields significantly better performance in predicting final outcome (AUC=0.88±0.12) than generalized linear model (AUC=0.78±0.12; P=0.005), CNNTmax (AUC=0.72±0.14; P<0.003), and ADCthres (AUC=0.66±0.13; P<0.0001) and a substantially better performance than CNNshallow (AUC=0.85±0.11; P=0.063). Measured by contrast, CNNdeep improves the predictions significantly, showing superiority to all other methods (P≤0.003). CNNdeep also seems to be able to differentiate outcomes based on treatment strategy with the volume of final infarct being significantly different (P=0.048). The considerable prediction improvement accuracy over current state of the art increases the potential for automated decision support in providing recommendations for personalized treatment plans.

Does tranexamic acid lead to changes in MRI measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? Protocol for a MRI substudy nested within the double-blind randomised controlled TICH-2 trial

ObjectivesTo test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI-defined hyperintense ischaemic lesions (primary hypothesis)...

Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome.

Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor. To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor. Retrospective. Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T. T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T. An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year. Statistical significance was assessed using the Wilcoxon two-tailed rank test. The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure. In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

Optimal Timing of Surgery for Intramedullary Cavernous Hemangioma of the Spinal Cord in Relation to Preoperative Motor Paresis, Disease Duration, and Tumor Volume and Location.

Study Design:Prospective study.Objective:Investigate factors associated with preoperative motor paresis, recovery, ambulatory status, and intraoperative neurophysiological monitoring (IONM) among patients with no preoperative paresis (N group), complete preoperative motor recovery (CR group), and no complete recovery (NCR group) in patients with intramedullary spinal cavernous hemangioma to determine the optimal timing of surgery.Methods:The study evaluated 41 surgical cases in our institute. Disease duration, tumor lesion, manual muscle testing (MMT), and gait at onset, just before surgery, and final follow-up (FU), tumor and lesion volume, IONM, extent of tumor resection, and tumor recurrence were evaluated among N, CR, and NCR groups.Results:Motor paresis at onset was found in 26 patients (63%), with 42% of those in CR group. Disease duration from onset negatively affected stable gait just before surgery and FU as well as lower preoperative MMT (P < .05). Thoracic tumors were associated with patients with unstable gait before surgery (P < .05). Tumor volume was larger in NCR group (P < .05). IONM significantly decreased in NCR and CR groups than in N group (P < .05). The NCR group had residual mild motor paresis at FU (P < .05). Stable gait at FU was similar in N group and CR group, though lower in NCR group (P < .05).Conclusions:Early surgery is generally recommended for thoracic tumors and large tumors during stable gait without motor paresis before long disease duration. Surgery may be postponed until patients recover from preoperative motor paresis to allow optimal surgical outcome. IONM should be carefully monitored in patients with a history of preoperative paresis even with preoperative complete motor recovery.

Distal Middle Cerebral Artery Branch Recanalization Does Not Affect Final Lesion Volume in Ischemic Stroke

Background: Early recanalization in ischemic stroke is associated with favorable outcome. However, limited data are available on the effect of recanalization on infarct growth and functional outcome in stroke with distal middle cerebral artery (MCA) pathology. This study was aimed at determining the effect of recanalization in acute stroke patients with perfusion-diffusion mismatch and occlusion or high-grade stenosis of a distal MCA branch. Methods: We prospectively examined 34 consecutive stroke patients with perfusion-diffusion mismatch and M3 or M4 pathology within 24 h of symptom onset. The MRI protocol consisted of diffusion-weighted images (DWI), fluid-attenuated inversion recovery (FLAIR), T2*, perfusion-weighted imaging, time-of-flight magnetic resonance angiography at days 0, 1, and 4-6. Volume measurements were performed with MRIcron. Infarct growth was defined as the difference between lesion volumes on FLAIR at days 4-6 and DWI at day 0. Certified raters assessed modified Rankin Scale scores at discharge and day 90. Results: Twenty-four patients (71%) showed recanalization at day 1. Infarct growth was modest (median 2.4 mL, 95% CI 0.8-6.7) and not significantly different between patients with and without recanalization (p = 0.87). Functional outcome at discharge was good with 70% of patients suffering no significant disabilities. There was no association between functional outcome at discharge and recanalization (OR 2.1, 95% CI 0.4-13.0, p = 0.40) or infarct volume at days 4-6 (p = 0.40). Conclusions: The high rate of spontaneous recanalization and good functional outcome in patients with distal MCA pathology might obscure a potential benefit from recanalization in this population.