Radiology Publications

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https://hdl.handle.net/20.500.14038/198

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The mission of the Department of Radiology at UMass Chan Medical School is to bring scientific advances in medical imaging to clinical application. This collection showcases journal articles and other publications written by faculty and researchers of the Department of Radiology.

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Natural history progression of MRI brain volumetrics in type II late-infantile and juvenile GM1 gangliosidosis patients
(2025-01-19) Kolstad, Josephine; Zoppo, Christopher; Johnston, Jean M; D'Souza, Precilla; Kühn, Anna Luisa; Vardar, Zeynep; Peker, Ahmet; Hader, Asma; Celik, Hakki; Lewis, Connor J; Lindsay, Clifford; Rentiya, Zubir S; Lebel, Catherine; Vedantham, Srinivasan; Vachha, Behroze; Gray-Edwards, Heather L; Acosta, Maria T; Tifft, Cynthia J; Shazeeb, Mohammed Salman; Radiology
Objective: GM1 gangliosidosis is a rare lysosomal storage disorder characterized by the accumulation of GM1 gangliosides in neuronal cells, resulting in severe neurodegeneration. Currently, limited data exists on the brain volumetric changes associated with this disease. This study focuses on the late-infantile and juvenile subtypes of type II GM1 gangliosidosis, aiming to quantify brain volumetric characteristics to track disease progression. Methods: Brain volumetric analysis was conducted on 56 MRI scans from 24 type II GM1 patients (8 late-infantile and 16 juvenile) and 19 healthy controls over multiple time points. The analysis included the use of semi-automated segmentation of the whole brain, ventricles, cerebellum, corpus callosum, thalamus, caudate, and lentiform nucleus. A generalized linear model was used to compare the volumetric measurements between the patient groups and healthy controls, accounting for age as a confounding factor. Results: Both late-infantile and juvenile GM1 patients exhibited significant whole-brain atrophy compared to healthy controls, even after adjusting for age. Notably, the late-infantile subtype displayed more pronounced atrophy in the cerebellum, thalamus, and corpus callosum compared to the juvenile subtype. Both late-infantile and juvenile subtypes showed significantly higher ventricular volumes and a significant reduction in all other structure volumes compared to the healthy controls. The volumetric measurements also correlated well with disease severity based on clinical metrics. Conclusions: The findings underscore the distinct brain volumetrics of the late-infantile and juvenile subtypes of GM1 gangliosidosis compared to healthy controls. These quantifications can be used as reliable imaging biomarkers to track disease progression and evaluate responses to therapeutic interventions.
Impact of smoking on recurrence rates among wide-neck intracranial aneurysms treated with Woven EndoBridge: a multicenter retrospective study
(2025-01-31) Vaishnav, Dhrumil; Essibayi, Muhammed Amir; Musmar, Basel; Adeeb, Nimer; Salim, Hamza Adel; Aslan, Assala; Cancelliere, Nicole M; McLellan, Rachel M; Algin, Oktay; Ghozy, Sherief; Lay, Sovann V; Guenego, Adrien; Renieri, Leonardo; Carnevale, Joseph; Saliou, Guillaume; Mastorakos, Panagiotis; El Naamani, Kareem; Shotar, Eimad; Premat, Kevin; Möhlenbruch, Markus; Kral, Michael; Doron, Omer; Chung, Charlotte; Salem, Mohamed M; Lylyk, Ivan; Foreman, Paul M; Vachhani, Jay A; Shaikh, Hamza; Župančić, Vedran; Hafeez, Muhammad U; Catapano, Joshua; Waqas, Muhammad; Ayberk, Giyas; Celal Gunes, Yasin; Rabinov, James D; Ren, Yifan; Schirmer, Clemens M; Piano, Mariangela; Kühn, Anna L; Michelozzi, Caterina; Elens, Stéphanie; Starke, Robert M; Hassan, Ameer E; Ogilvie, Mark; Nguyen, Anh; Jones, Jesse; Brinjikji, Waleed; Nawka, Marie T; Psychogios, Marios; Ulfert, Christian; Diestro, Jose Danilo Bengzon; Pukenas, Bryan; Burkhardt, Jan-Karl; Huynh, Thien; Martinez-Gutierrez, Juan Carlos; Sheth, Sunil A; Spiegel, Gary; Tawk, Rabih G; Lubicz, Boris; Panni, Pietro; Puri, Ajit S; Pero, Guglielmo; Nossek, Erez; Raz, Eytan; Killer-Oberpfalzer, Monika; Griessenauer, Christoph J; Asadi, Hamed; Siddiqui, Adnan; Brook, Allan L; Haranhalli, Neil; Ducruet, Andrew F; Albuquerque, Felipe C; Regenhardt, Robert W; Stapleton, Christopher J; Kan, Peter; Kalousek, Vladimir; Lylyk, Pedro; Boddu, Srikanth; Knopman, Jared; Aziz-Sultan, Mohammad A; Tjoumakaris, Stavropoula I; Clarençon, Frédéric; Limbucci, Nicola; Cuellar-Saenz, Hugo H; Jabbour, Pascal M; Mendes Pereira, Vitor; Patel, Aman B; Altschul, David J; Dmytriw, Adam A; Radiology
Objective: Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. Methods: A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. Results: Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69-2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70-2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). Conclusions: This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.
Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin
(2025-01-28) Salim, Hamza A; Yedavalli, Vivek; Milhem, Fathi; Musmar, Basel; Adeeb, Nimer; Daraghma, Motaz; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kuhn, Anna; Khalife, Jane; Ghozy, Sherief; Scarcia, Luca; Tan, Benjamin Yq; Regenhardt, Robert; Heit, Jeremy; Cancelliere, Nicole Mariantonia; Bernstock, Joshua; Rouchaud, Aymeric; Fiehler, Jens; Sheth, Sunil A; Puri, Ajit S; Dyzmann, Christian; Colasurdo, Marco; Renieri, Leonardo; Filipe, João Pedro; Harker, Pablo; Radu, Răzvan Alexandru; Abdalkader, Mohamad; Klein, Piers; Marrota, Thomas; Spears, Julian; Ota, Takahiro; Mowla, Ashkan; Jabbour, Pascal; Biswas, Arundhati; Clarencon, Frederic; Siegler, James E; Nguyen, Thanh N; Varela, Ricardo; Baker, Amanda; Essibayi, Muhammed Amir; Altschul, David; Gonzalez, Nestor; Möhlenbruch, Markus; Costalat, Vincent; Gory, Benjamin; Stracke, Christian; Hecker, Constantin; Shaikh, Hamza; Griessenaur, Christoph; Liebeskind, David S; Pedicelli, Alessandro; Alexandre, Andrea; Tancredi, Illario; Faizy, Tobias Djamsched; Kalsoum, Erwah; Wintermark, Max; Lubicz, Boris; Patel, Aman B; Pereira, Vitor Mendes; Guenego, Adrien; Dmytriw, Adam; Neurology; Radiology
Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (mRS 0-2). Secondary outcomes included excellent functional outcome at 90 days (mRS 0-1), mortality, and day-one post-MT NIHSS score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1,354 patients, 150 were on pre-stroke low-dose aspirin. After applying Inverse Probability of Treatment Weighting (IPTW), Aspirin use was associated with significantly better functional outcomes (mRS 0-2: OR =1.89 , 95% CI, 1.14 to 3.12 ) and lower 90-day mortality (OR = 0.56, 95% CI, 0.32 to 1.00). The aspirin group had lower NIHSS scores on day one (β = -1.5, 95% CI, -2.8 to - 0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI, 0.60 to 1.43). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.
Tenzing Assisted Delivery of Aspiration (TADA) technique for thrombectomy of medium vessel occlusions using the Freeclimb 54 catheter: multicenter experience
(2025-01-23) Settecase, Fabio; Puri, Ajit S; Lee, Shane Sh; Khangura, Rajkamal S; Budzik, Ronald F; Pema, Peter J; Chaudury, Thymur; Page, Matthew J; McGuinness, Ben J; Colasurdo, Marco; Tonetti, Daniel A; Grossberg, Jonathan A; Singh, Jasmeet; Kuhn, Anna Luisa; Alexander, Matthew D; Varjavand, Bahram; Priest, Ryan A; Kim, JaeHyun; Baxter, Blaise W; Kim, Warren T; English, Joey D; Caldwell, James; Radiology
Background: Medium vessel occlusions (MeVOs) account for 25-40% of acute ischemic stroke. The Tenzing 5 (Route 92 Medical, San Mateo, California, USA) and FreeClimb 54 (Route 92 Medical, San Mateo, California, USA) catheter is a novel delivery-aspiration catheter combination designed to facilitate aspiration thrombectomy (AT) of MeVOs. We report our clinical experience using the Tenzing assisted delivery of aspiration (TADA) technique with FreeClimb 54 for first-line AT of MeVO. Methods: We retrospectively reviewed consecutive patients who underwent MeVO first-line AT using TADA with FreeClimb 54 at nine institutions in the USA and one in New Zealand. Results: 94 MeVOs (65 primary, 29 secondary) were treated in 92 patients: median age 71 (IQR 58-81) years; 49/92 (53%) women. FreeClimb 54 was successfully delivered by Tenzing 5 to all 94/94 MeVOs: 26 proximal M2; 44 distal M2; 5 M3; 6 A2; 4 A3; and 8 P2. Median target vessel diameter on DSA was 1.7 (IQR 1.4-1.8) mm. A leading microwire was used to advance Tenzing in 84% of cases. A stent retriever was used for additional thrombectomy passes in 6/94 (6%) patients. For a primary MeVO, final modified expanded Thrombolysis in Cerebral Infarction (meTICI) 2B-3 reperfusion was achieved in 63/65 (97%) patients, after a median of 1 (IQR 1-2) pass, with a first pass effect (FPE, meTICI 2C-3) in 43/65 (66%). Secondary MeVO FPE (eTICI 2C-3) was achieved in 20/29 (69%) patients. Tenzing 5-FreeClimb 54 related complications occurred in 2/94 (2%) patients: one perforation with asymptomatic subarachnoid hemorrhage and one embolus to new territory. Conclusions: MeVO first-line AT using the TADA technique with Tenzing 5 and FreeClimb 54 had a high FPE with a low complication rate.
Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory
(2025-01-23) Faizy, Tobias D; Yedavalli, Vivek; Salim, Hamza Adel; Lakhani, Dhairya A; Musmar, Basel; Adeeb, Nimer; Essibayi, Muhammed Amir; Daraghma, Motaz; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kuhn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; Scarcia, Luca; Yeo, Leonard Ll; Tan, Benjamin Yq; Regenhardt, Robert W; Heit, Jeremy Josef; Cancelliere, Nicole M; Rouchaud, Aymeric; Fiehler, Jens; Sheth, Sunil A; Puri, Ajit S; Dyzmann, Christian; Colasurdo, Marco; Renieri, Leonardo; Filipe, João Pedro; Harker, Pablo; Radu, Răzvan Alexandru; Abdalkader, Mohamad; Klein, Piers; Marotta, Thomas R; Spears, Julian; Ota, Takahiro; Mowla, Ashkan; Jabbour, Pascal; Biswas, Arundhati; Clarençon, Frédéric; Siegler, James E; Nguyen, Thanh N; Varela, Ricardo; Baker, Amanda; Altschul, David; Gonzalez, Nestor; Möhlenbruch, Markus A; Costalat, Vincent; Gory, Benjamin; Stracke, Christian Paul; Hecker, Constantin; Marnat, Gaultier; Shaikh, Hamza; Griessenauer, Christoph J; Liebeskind, David S; Pedicelli, Alessandro; Alexandre, Andrea Maria; Tancredi, Illario; Kalsoum, Erwah; Wintermark, Max; Lubicz, Boris; Patel, Aman B; Mendes Pereira, Vitor; Dmytriw, Adam A; Guenego, Adrien; Radiology
Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0-2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results: Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0-1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion: Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.
Comparative analysis of deep learning and radiomic signatures for overall survival prediction in recurrent high-grade glioma treated with immunotherapy
(2025-01-21) Wan, Qi; Lindsay, Clifford; Zhang, Chenxi; Kim, Jisoo; Chen, Xin; Li, Jing; Huang, Raymond Y; Reardon, David A; Young, Geoffrey S; Qin, Lei; Radiology
Background: Radiomic analysis of quantitative features extracted from segmented medical images can be used for predictive modeling of prognosis in brain tumor patients. Manual segmentation of the tumor components is time-consuming and poses significant reproducibility issues. We compare the prediction of overall survival (OS) in recurrent high-grade glioma(HGG) patients undergoing immunotherapy, using deep learning (DL) classification networks along with radiomic signatures derived from manual and convolutional neural networks (CNN) automated segmentation. Materials and methods: We retrospectively retrieved 154 cases of recurrent HGG from multiple centers. Tumor segmentation was performed by expert radiologists and a convolutional neural network (CNN). From the segmented tumors, 2553 radiomic features were extracted for each case. A robust feature subset was selected using intraclass correlation coefficient analysis between manual and automated segmentations. The data was divided into a 9:1 ratio and validated through ten-fold cross-validation and tested on a rotating test set. Features selection was done by the Kruskal-Wallis test. The Radiomics-based OS predictions, generated using Support Vector Machine (SVM), were compared between the two segmentation approaches and against OS prediction by the CNN model adapted for classification. Model efficacy was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The clinical model AUC for OS prediction was 0.640 ± 0.013 (mean ± 95% confidence interval) in the training set and 0.610 ± 0.131 in the test set. The radiomics prediction of OS based on manual segmentation outperformed automatic segmentation (AUC of 0.662 ± 0.122 vs. 0.471 ± 0.086, respectively) in the test set. Robust features improved the performance of manual segmentation to AUC of 0.700 ± 0.102, of automated segmentation to 0.554 ± 0.085. The CNN prognosis model demonstrated promising results, with an average AUC of 0.755 ± 0.071 for training sets and 0.700 ± 0.101 for the test set. Conclusion: Manual segmentation-derived radiomic features outperformed automated segmentation-derived features for predicting OS in recurrent high-grade glioma patients undergoing immunotherapy. The end-to-end CNN prognosis model performed similarly to radiomics modeling using manual-segmentation-derived features without the need for segmentation. The potential time-saving must be weighed against the lower interpretability of end-to-end black box modeling.
Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study
(2025-01-15) Musmar, Basel; Salim, Hamza Adel; Adeeb, Nimer; Yedavalli, Vivek; Lakhani, Dhairya; El Naamani, Kareem; Henninger, Nils; Sundararajan, Sri Hari; Kühn, Anna Luisa; Khalife, Jane; Ghozy, Sherief; Scarcia, Luca; Tan, Benjamin Y Q; Regenhardt, Robert W; Heit, Jeremy J; Cancelliere, Nicole M; Bernstock, Joshua D; Rouchaud, Aymeric; Fiehler, Jens; Sheth, Sunil; Puri, Ajit S; Dyzmann, Christian; Colasurdo, Marco; Barreau, Xavier; Renieri, Leonardo; Filipe, João Pedro; Harker, Pablo; Radu, Răzvan Alexandru; Abdalkader, Mohamad; Klein, Piers; Marotta, Thomas R; Spears, Julian; Ota, Takahiro; Mowla, Ashkan; Jabbour, Pascal; Biswas, Arundhati; Clarençon, Frédéric; Siegler, James E; Nguyen, Thanh N; Varela, Ricardo; Baker, Amanda; Essibayi, Muhammed Amir; Altschul, David; Gonzalez, Nestor R; Möhlenbruch, Markus A; Costalat, Vincent; Gory, Benjamin; Stracke, Christian Paul; Aziz-Sultan, Mohammad Ali; Hecker, Constantin; Shaikh, Hamza; Liebeskind, David S; Pedicelli, Alessandro; Alexandre, Andrea M; Tancredi, Illario; Faizy, Tobias D; Kalsoum, Erwah; Lubicz, Boris; Patel, Aman B; Pereira, Vitor Mendes; Guenego, Adrien; Dmytriw, Adam A; Neurology; Radiology
Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored. Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7. Results: Of 443 patients, 51 (12%) had ASPECTS of 4-5, and 392 (88%) had scores of 6-7. The median age was 65 years (IQR: 46-79), with a balanced sex distribution between the groups. The most common site of initial occlusion was M2 branch in both groups (92% in ASPECTS 4-5 and 85% in ASPECTS 6-7) (p = 0.68). The ASPECTS 4-5 group had lower TICI 2c-3 achievement (31% vs. 55%, p = 0.002) and poorer functional outcomes (mRS 0-1 at 90 days: 12% vs. 29%, p = 0.03) compared to the ASPECTS 6-7 group. Intracranial hemorrhagic complications were higher in the ASPECTS 4-5 group (69% vs. 47%, p = 0.007). Multivariable analysis revealed ASPECTS 6-7 to be associated with higher odds of TICI 2c-3 (OR: 2.5; CI: 1.28 to 4.89, p = 0.007) and lower odds of intracranial hemorrhagic complications (OR: 0.4; CI: 0.19 to 0.81, p = 0.012). Conclusion: MT may be associated with improved outcomes in patients with moderate-to-low ASPECTS (6-7), though the lack of a control group limits definitive conclusions about its effectiveness. In patients with very low ASPECTS (4-5), higher rates of hemorrhagic complications and poorer outcomes were observed, but this does not necessarily preclude the use of MT. These findings highlight the need for further research and careful patient selection.
Paramagnetic rim lesion formation is predicted by the initial gadolinium-enhancing lesion diameter
(2025-01-17) Al Gburi, Mustafa; Mazzola, Maria; Absinta, Martina; Gaitán, María I; Reich, Daniel S; Dundamadappa, Sathish K; Hemond, Christopher C; Neurology; Radiology
Background: Paramagnetic rim lesions (PRLs) are a magnetic resonance imaging (MRI) marker of compartmentalized intraparenchymal inflammation. Objectives: The primary objective was to investigate clinical, demographic, and MRI factors that may be predictive of the future formation of PRL. Methods: This is a retrospective analysis of longitudinal data. Patients were included if they had ⩾1 gadolinium-enhancing lesion on any historical MRI and follow-up scan(s) ⩾6 months afterward on a standardized 3T MRI using the filtered phase component of a susceptibility-sensitive sequence ("SWAN"). Regression and machine-learning models were used to identify the predictive ability of demographic, clinical, immunological, treatment-related, and MRI predictors of PRL formation. Results: A total of 64 patients having 229 contrast-enhancing lesions (CELs) were included. Among all predictors, the diameter of the initial enhancing lesion was the most influential for determining subsequent PRL formation; every millimeter increase in diameter increased the risk of PRL formation by 44%. Other factors did not contribute additional information; the administration of steroids was not associated with any effect. Conclusions: The long-axis diameter of a CEL is the best translational predictor of subsequent PRL formation at follow-up. This measure holds promise as a method to identify patients at high risk of chronic active lesion formation during the acute inflammatory window.
A Method for Imaging the Ischemic Penumbra with MRI using IVIM
(2025-01-13) Liu, Mira M; Saadat, Niloufar; Roth, Steven P; Niekrasz, Marek A; Giurcanu, Mihai; Shazeeb, Mohammed Salman; Carroll, Timothy J; Christoforidis, Gregory A; Radiology
Background and purpose: In acute ischemic stroke, the amount of "local" CBF distal to the occlusion, i.e. all blood flow within a region whether supplied antegrade or delayed and dispersed through the collateral network, may contain valuable information regarding infarct growth rate and treatment response. DSC CBF using a local arterial input function (AIF) is one method of quantifying local CBF (local-qCBF) and correlates with collaterals. Similarly, intravoxel incoherent motion MRI (IVIM) is "local", with excitation and readout in the same plane, and a potential alternative way to measure local-qCBF. The purpose of this work was to compare IVIM local-qCBF against DSC local-qCBF in the ischemic penumbra, compare measurement of perfusion-diffusion mismatch (PWI/DWI), and examine if local-qCBF may improve prediction of final infarct. Materials and methods: Eight experiments in a pre-clinical canine model of middle cerebral artery occlusion were performed; native collateral circulation was quantified via x-ray DSA 30 minutes post-occlusion, and collateralization was subsequently enhanced in a subset of experiments with simultaneous pressor and vasodilator. IVIM and DSC MRI were acquired 2.5hr post-occlusion. IVIM was post-processed to return local-qCBF from fD*, water transport time (WTT) from D*, diffusion from D, and the PWI/DWI mismatch. These were compared with DSC parameters processed first with a standard global-AIF and then with a local-AIF. These DSC parameters included time-to-maximum, local MTT, standard-qCBF, local-qCBF and PWI/DWI mismatch. Infarct volume was measured with DWI at 2.5hrs and 4hrs post-occlusion. Results: 2.5hr post-occlusion, IVIM local-qCBF in the non-infarcted ipsilateral territory strongly correlated with DSC local-qCBF (slope=1.00, R2=0.69, Lin's CCC=0.71). Correlation was weaker between IVIM local-qCBF and DSC standard-qCBF (R2=0.13). DSC localqCBF and IVIM local-qCBF in the non-infarcted ipsilateral territory both returned strong prediction of final infarct volume (R2=0.78, R2=0.61 respectively). DSC standard-qCBF was a weaker predictor (R2=0.12). The hypoperfused lesion from DSC local-qCBF and from IVIM local-qCBF both predicted final infarct volume with good sensitivity and correlation (slope=2.08, R2=0.67, slope=2.50, R2=0.68 respectively). The IVIM PWI/DWI ratio was correlated with infarct growth (R2=0.70) and WTT correlated with DSC MTT (R2=0.60). Conclusions: Non-contrast IVIM measurement of local-qCBF and PWI/DWI mismatch may include collateral circulation and improve prediction of infarct growth.
A Novel Method for the Generation of Realistic Lung Nodules Visualized Under X-Ray Imaging
(2024-12-05) Peker, Ahmet; Sinha, Ayushi; King, Robert M; Minnaard, Jeffrey; Sterren, William van der; Bydlon, Torre; Bankier, Alexander A; Gounis, Matthew J; Radiology
Objective: Image-guided diagnosis and treatment of lung lesions is an active area of research. With the growing number of solutions proposed, there is also a growing need to establish a standard for the evaluation of these solutions. Thus, realistic phantom and preclinical environments must be established. Realistic study environments must include implanted lung nodules that are morphologically similar to real lung lesions under X-ray imaging. Methods: Various materials were injected into a phantom swine lung to evaluate the similarity to real lung lesions in size, location, density, and grayscale intensities in X-ray imaging. A combination of n-butyl cyanoacrylate (n-BCA) and ethiodized oil displayed radiopacity that was most similar to real lung lesions, and various injection techniques were evaluated to ensure easy implantation and to generate features mimicking malignant lesions. Results: The techniques used generated implanted nodules with properties mimicking solid nodules with features including pleural extensions and spiculations, which are typically present in malignant lesions. Using only n-BCA, implanted nodules mimicking ground glass opacity were also generated. These results are condensed into a set of recommendations that prescribe the materials and techniques that should be used to reproduce these nodules. Conclusions: Generated recommendations on the use of n-BCA and ethiodized oil can help establish a standard for the evaluation of new image-guided solutions and refinement of algorithms in phantom and animal studies with realistic nodules.
CT-guided Left Stellate Ganglion Cryoneurolysis for Refractory Ventricular Arrhythmias
(2024-12) Li, Ningcheng; Kim, Junman; Patel, Anshul M; Markham, David W; Tompkins, Christine M; Rahban, Youssef; Stokken, Glenn; Gottbrecht, Matthew; Prologo, Frank J; Resnick, Neil J; Medicine; Radiology
Background Ventricular arrhythmias (VAs), including ventricular tachycardia and ventricular fibrillation, present substantial therapeutic challenges due to their high morbidity, mortality, and increasing prevalence. Current treatments often prove infeasible or inadequate in patients with refractory VAs. Purpose To evaluate the safety and effectiveness of CT-guided left stellate ganglion cryoneurolysis (SGC) in the treatment of refractory VAs. Materials and Methods This retrospective study reviewed all consecutive patients with refractory VAs who underwent SGC between June 2020 and December 2023 at two tertiary care centers. Patients with refractory VAs who underwent CT-guided left SGC were included. No patients were excluded. Data on preprocedural clinical status, procedural approach, procedural outcomes, and adverse events were analyzed. The pre- and postprocedural number of defibrillations were compared using the Wilcoxon matched-pairs signed rank test. Results A total of 17 patients (mean age, 60.4 years ± 2.7 [standard error of the mean]; 14 male) were included; seven patients (41%) were receiving β-adrenergic blocking agents. The mean number of antiarrhythmic medications per patient was 2.2 ± 0.2. CT-guided left SGC led to a significant reduction in defibrillations, from a median of 3 (IQR, 3-15) to 0 (IRQ, 0-0) in the 24 hours before and after the procedure, respectively ( < .001). Clinical success, defined as freedom from defibrillation within the preceding 24-hour period, was achieved in 14 of 17 patients (82%) 24 hours after and 15 of 17 patients (88%) 72 hours after the procedure. Of 17 patients, 12 (71%) proceeded to additional procedural management after SGC. At a mean follow-up of 469.2 days ± 90.8, 14 of 17 patients (82%) were alive. No moderate or high-grade adverse events were observed; mild adverse events included left upper extremity neurapraxia ( = 1) and transient Horner syndrome ( = 3). Conclusion CT-guided left SGC demonstrated promising effectiveness and safety in treating patients with refractory VAs. Thus, SGC warrants consideration for inclusion in a multidisciplinary treatment algorithm for VAs. © RSNA, 2024 See also the editorial by Cadour and Scemama in this issue.
Flow-diverting stents for the treatment of unruptured distal anterior cerebral artery aneurysms: analysis of the CRETA Registry
(2024-12-18) Scarcia, Luca; Clarençon, Frédéric; Dmytriw, Adam A; Shotar, Eimad; Premat, Kevin; Jabbour, Pascal; Tjoumakaris, Stavropoula I; Gooch, Reid; Psychogios, Marios-Nikos; Ntoulias, Nikolaos; Sporns, Peter B; Puri, Ajit S; Singh, Jasmeet; Kuhn, Anna Luisa; Hassan, Ameer E; Algin, Oktay; Möhlenbruch, Markus A; Hohenstatt, Sophia; Russo, Riccardo; Bergui, Mauro; Goren, Oded; Kole, Matthew J; Bankole, Nourou Dine Adeniran; Bibi, Richard; Boulouis, Gregoire; Morimoto, Takeshi; Sakakibara, Fumihiro; Pop, Raoul; Juravle, Ciprian; Ho, Joanna Wk; Ferrario, Angel; Pujol Lereis, Virginia; Cooper, Jared; Gandhi, Chirag D; Salsano, Giancarlo; Castellan, Lucio; Camilli, Arianna; Consoli, Arturo; Sgreccia, Alessandro; Raz, Eytan; Chung, Charlotte; Burel, Julien; Papagiannaki, Chrysanthi; Rasheed, Umair; Baqir Hassan, Khawaja Muhammad; Hong, Tao; Ji, Zhe; Rautio, Riitta; Sinislao, Matias; Ruggiero, Maria; Lafe, Elvis; Da Ros, Valerio; Bellini, Luigi; Gabrieli, Joseph D; Cester, Giacomo; Levitt, Michael R; Carroll, Kate T; Abecassis, Zack A; Caragliano, Antonio Armando; Vinci, Sergio L; Bellanger, Guillaume; Cognard, Christophe; Marnat, Gaultier; Saleille, Lisa; Limbucci, Nicola; Capasso, Francesco; Piano, Mariangela; Rollo, Claudia; Guedon, Alexis; Arpaia, Francesco; Romi, Andrea; Di Caterino, Fortunato; Biondi, Alessandra; Kalsoum, Erwah; Mykola, Vyval; Guenego, Adrien; Patel, Aman B; Pereira, Vitor M; Pedicelli, Alessandro; Alexandre, Andrea Maria; Radiology
Background: Data about the safety and the efficacy of flow diversion for distal anterior cerebral artery (DACA) aneurysms are limited. We present the largest multicenter analysis evaluating the outcomes of flow diversion in unruptured DACA aneurysm treatment. Methods: Databases from 39 centers were retrospectively reviewed for unruptured DACA aneurysms treated with flow-diverting stents. Demographics, clinical presentation, radiographic characteristics, procedural complications, and outcomes were assessed. Results: A total of 168 patients with 168 unruptured DACA aneurysms were treated between January 2018 and December 2022. One hundred and twenty-five were women (74.4%) and the median age was 61 (IQR 52-67) years. The most common morphology was saccular (91.7%), with branch involvement in 61.9% of cases. Median parent vessel diameter was 1.9 mm (IQR 1.7-2.2) and stents were successfully deployed in 99.4% of cases. In 96.4% a single stent was implanted, while 3.6% of cases required two stents. Median imaging follow-up was 16.5 (IQR 7-24) months. At last follow-up the rate of occlusion (O'Kelly-Marotta scale C or D) was 82.1%. Symptomatic thromboembolic or hemorrhagic complications occurred in 5.3% of patients and the mortality rate was 0.6%. The rate of retreatment was 1.2%. Conclusions: Flow-diverting stents are a reasonably safe and effective treatment option for unruptured DACA aneurysms.
Resting-State Functional MRI: Current State, Controversies, Limitations, and Future Directions- AJR Expert Panel Narrative Review
(2024-12-11) Vachha, Behroze A; Kumar, Vinodh A; Pillai, Jay J; Shimony, Joshua; Tanabe, Jody; Sair, Haris I; Radiology
Resting-state functional MRI (rs-fMRI), a promising method for interrogating different brain functional networks from a single MRI acquisition, is increasingly utilized in clinical presurgical and other pretherapeutic brain mapping. However, challenges in standardization of acquisition, preprocessing, and analysis methods across centers, and variability in results interpretation, complicate its clinical use. Additionally, inherent problems regarding reliability of language lateralization, interpatient variability of cognitive network representation, dynamic aspects of intranetwork and internetwork connectivity, and effects of neurovascular uncoupling on network detection still must be overcome. Although deep-learning solutions and further methodologic standardization will help address these issues, rs-fMRI remains generally considered an adjunct to task-based fMRI (tb-fMRI) for clinical presurgical mapping. Nonetheless, in many clinical instances, rs-fMRI may offer valuable additional information that supplements tb-fMRI, especially if tb-fMRI is inadequate due to patient performance or other limitations. Future growth in clinical applications of rs-fMRI is anticipated as challenges are increasingly addressed. In this AJR Expert Panel Narrative Review, we summarize the current state and emerging clinical utility of rs-fMRI, focusing on its role in presurgical mapping. We present ongoing controversies and limitations in clinical applicability and discuss future directions including the developing role of rs-fMRI in neuromodulation treatment for various neurologic disorders.
EXCELLENT Registry: A Prospective, Multicenter, Global Registry of Endovascular Stroke Treatment With the EMBOTRAP Device
(2024-11-19) Nogueira, Raul G; Andersson, Tommy; Haussen, Diogo C; Yoo, Albert J; Hanel, Ricardo A; Zaidat, Osama O; Hacke, Werner; Jovin, Tudor G; Fiehler, Jens; De Meyer, Simon F; Brinjikji, Waleed; Doyle, Karen M; Kallmes, David F; Liebeskind, David S; Virmani, Renu; Kokoszka, Malgosia A; Inoa, Violiza; Humphries, William; Woodward, Keith B; Jabbour, Pascal M; François, Olivier; Levy, Elad I; Bozorgchami, Hormozd; Boor, Stephan; Cohen, Jose E; Dashti, Shervin R; Taqi, Muhammad A; Budzik, Ronald F; Schirmer, Clemens M; Hussain, M Shazam; Estrade, Laurent; De Leacy, Reade A; Puri, Ajit S; Chitale, Rohan V; Brekenfeld, Caspar; Siddiqui, Adnan H; Radiology
Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P<0.001), pointing to a potential preprocedure indicator of challenging clot. Conclusions: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578.
Investigation of scatter energy window width and count levels for deep learning-based attenuation map estimation in cardiac SPECT/CT imaging
(2024-11-11) Chen, Yuan; Pretorius, P Hendrik; Yang, Yongyi; King, Michael A; Lindsay, Clifford; Radiology
Deep learning (DL) is becoming increasingly important in generating attenuation maps for accurate attenuation correction (AC) in cardiac perfusion SPECT imaging. Typically, DL models take inputs from initial reconstructed SPECT images, which are performed on the photopeak window and often also on scatter windows. While prior studies have demonstrated improvements in DL performance when scatter window images are incorporated into the DL input, the comprehensive analysis of the impact of employing different scatter windows remains unassessed. Additionally, existing research mainly focuses on applying DL to SPECT scans obtained at clinical standard count levels. This study aimed to assess utilities of DL from two aspects: (1) investigating the impact when different scatter windows were used as input to DL, and (2) evaluating the performance of DL when applied on SPECT scans acquired at a reduced count level.We utilized 1517 subjects, with 386 subjects for testing and the remaining 1131 for training and validation.The results showed that as scatter window width increased from 4% to 30%, a slight improvement was observed in DL estimated attenuation maps. The application of DL models to quarter-count (¼-count) SPECT scans, compared to full-count scans, showed a slight reduction in performance. Nonetheless, discrepancies across different scatter window configurations and between count levels were minimal, with all normalized mean square error (NMSE) values remaining within 2.1% when comparing the different DL attenuation maps to the reference CT maps. For attenuation corrected SPECT slices using DL estimated maps, NMSE values were within 0.5% when compared to CT correction.This study, leveraging an extensive clinical dataset, showed that the performance of DL seemed to be consistent across the use of varied scatter window settings. Moreover, our investigation into reduced count studies indicated that DL could provide accurate AC even at a ¼-count level.
Aging, HIV infection, and alcohol exert synergist effects on regional thalamic volumes resulting in functional impairment
(2024-10-12) Pfefferbaum, Adolf; Zahr, Natalie M; Sassoon, Stephanie A; Fama, Rosemary; Saranathan, Manojkumar; Pohl, Kilian M; Sullivan, Edith V; Radiology
Objective: Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50 % living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown is whether aging with HIV affects thalamic nuclei and associated functions differentially and whether the common comorbidity of alcohol use disorder (AUD) + HIV accelerates aging. Methods: This mixed cross-sectional/longitudinal design examined 216 control, 69 HIV, and 74 HIV + AUD participants, age 25-75 years old at initial visit, examined 1-8 times. MRI thalamic volumetry, parcellated using THalamus Optimized Multi-Atlas Segmentation (THOMAS), identified 10 nuclei grouped into 4 functional regions for correlation with age and measures of neuropsychological, clinical, and hematological status. Results: Aging in the control group was best modeled with quadratic functions in the Anterior and Ventral regions and with linear functions in the Medial and Posterior regions. Relative to controls, age-related decline was even steeper in the Anterior and Ventral regions of the HIV group and in the Anterior region of the comorbid group. Anterior volumes of each HIV group declined significantly faster after age 50 (HIV = -2.4 %/year; HIV + AUD = -2.8 %/year) than that of controls (-1.8 %/year). Anterior and Ventral volumes were significantly smaller in the HIV + AUD than HIV-only group when controlling for infection factors. Although compared with controls HIV + AUD declined faster than HIV alone, the two HIV groups did not differ significantly from each other in aging rates. Declining Attention/Working Memory and Motor Skills performance correlated with Anterior and Posterior volume declines in the HIV + AUD group. Conclusions: Regional thalamic volumetry detected normal aging declines, differential and accelerated volume losses in HIV, relations between age-related nuclear and performance declines, and exacerbation of volume declines in comorbid AUD contributing to functional deficits.
Outcomes and relapse patterns in primary central nervous system lymphoma: Longitudinal analysis of 559 patients diagnosed from 1983 to 2020
(2024-11-04) Tringale, Kathryn R; Scordo, Michael; Yahalom, Joachim; White, Charlie; Zhang, Zhigang; Vachha, Behroze; Cederquist, Gustav; Schaff, Lauren; DeAngelis, Lisa; Grommes, Christian; Imber, Brandon S; Radiology
Background: Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up. Methods: T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. Results: Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status [KPS] ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval [95% CI]: 76%-84%) and 46% (95% CI: 41%-53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%-3.27%) was associated with local relapse in refractory patients. Conclusions: We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.
A roadmap towards standardized neuroimaging approaches for human thalamic nuclei
(2024-10-17) Segobin, Shailendra; Haast, Roy A M; Kumar, Vinod Jangir; Lella, Annalisa; Alkemade, Anneke; Bach Cuadra, Meritxell; Barbeau, Emmanuel J; Felician, Olivier; Pergola, Giulio; Pitel, Anne-Lise; Saranathan, Manojkumar; Tourdias, Thomas; Hornberger, Michael; Radiology
The thalamus has a key role in mediating cortical-subcortical interactions but is often neglected in neuroimaging studies, which mostly focus on changes in cortical structure and activity. One of the main reasons for the thalamus being overlooked is that the delineation of individual thalamic nuclei via neuroimaging remains controversial. Indeed, neuroimaging atlases vary substantially regarding which thalamic nuclei are included and how their delineations were established. Here, we review current and emerging methods for thalamic nuclei segmentation in neuroimaging data and consider the limitations of existing techniques in terms of their research and clinical applicability. We address these challenges by proposing a roadmap to improve thalamic nuclei segmentation in human neuroimaging and, in turn, harmonize research approaches and advance clinical applications. We believe that a collective effort is required to achieve this. We hope that this will ultimately lead to the thalamic nuclei being regarded as key brain regions in their own right and not (as often currently assumed) as simply a gateway between cortical and subcortical regions.
Quantifying and mitigating motor phenotypes induced by antisense oligonucleotides in the central nervous system
(2024-10-28) Moazami, Michael P; Rembetsy-Brown, Julia M; Sarli, Samantha L; McEachern, Holly R; Wang, Feng; Ohara, Masahiro; Wagh, Atish; Kelly, Karen; Krishnamurthy, Pranathi Meda; Weiss, Alexandra; Marosfoi, Miklos; King, Robert M; Motwani, Mona; Gray-Edwards, Heather; Fitzgerald, Katherine A; Brown, Robert H; Watts, Jonathan K; RNA Therapeutics Institute; Neurology; Radiology; Program in Innate Immunity; Medicine; Biochemistry and Molecular Biotechnology
Antisense oligonucleotides (ASOs) are emerging as a promising class of therapeutics for neurological diseases. When injected directly into cerebrospinal fluid, ASOs distribute broadly across brain regions and exert long-lasting therapeutic effects. However, many phosphorothioate (PS)-modified gapmer ASOs show transient motor phenotypes when injected into the cerebrospinal fluid, ranging from reduced motor activity to ataxia or acute seizure-like phenotypes. Using a behavioral scoring assay customized to reflect the timing and nature of these effects, we show that both sugar and phosphate modifications influence acute motor phenotypes. Among sugar analogs, DNA induces the strongest motor phenotypes while 2'-substituted RNA modifications improve the tolerability of PS ASOs. Reducing the PS content of gapmer ASOs, which contain a stretch of PS-DNA, improves their toxicity profile, but in some cases also reduces efficacy or duration of effect. We show that this acute toxicity is not mediated by major nucleic acid sensing immune pathways. Formulating ASOs with divalent ions before injection and avoiding phosphate-based buffers modestly improved tolerability through mechanisms at least partially distinct from reduced PS content. Overall, our work identifies and quantifies an understudied aspect of oligonucleotide toxicology in the CNS, explores its mechanism, and presents platform-level medicinal chemistry and formulation approaches that improve tolerability of this class of compounds.
Clinical and biochemical abnormalities in a feline model of GM2 activator deficiency
(2024-11-29) Beecy, Sidney J; Gross, Amanda L; Maguire, Anne S; Hoffman, Leah M K; Diffie, Elise B; Cuddon, Paul; Kell, Pamela; Jiang, Xuntian; Gray-Edwards, Heather L; Martin, Douglas R; Horae Gene Therapy Center; Radiology
Though it has no catalytic activity toward GM2 ganglioside, the GM2 activator protein (GM2A) is essential for ganglioside hydrolysis by facilitating the action of lysosomal ß-N-acetylhexosaminidase. GM2A deficiency results in death in early childhood due to rapid central nervous system deterioration similar to the related GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease. This manuscript further characterizes a feline model of GM2A deficiency with a focus on clinical and biochemical parameters that may be useful as benchmarks for translational therapeutic research. The GM2A deficient cat has clinical features consistent with the human condition, including isointensity of gray and white matter of the brain on T2-weighted MRI; MR spectroscopic changes of brain metabolites consistent with gliosis, neuronal injury and demyelination; rhythmical slowing of cerebral cortical activation on electroencephalography; and elevation of aspartate aminotransferase and lactate dehydrogenase in cerebrospinal fluid. Biochemically, the brain of GM2A deficient cats has storage of GM2 and GA2 ganglioside coincident with increased hexosaminidase activity toward a standard synthetic substrate. Also, the brain of GM2A deficient cats has increased levels of lyso-platelet activating factor and lyso-phosphatidylcholine, which may serve as novel biomarkers of disease progression and provide insights into pathogenic mechanisms.

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