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Article ; Online: Prognostic Neuroimaging Biomarkers in Acute Vascular Brain Injury and Traumatic Brain Injury.

Krawchuk, Lindsey J / Sharrock, Matthew F

2023 Volume 43, Issue 5, Page(s) 699–711

Abstract: Prognostic imaging biomarkers after acute brain injury inform treatment decisions, track the progression of intracranial injury, and can be used in shared decision-making processes with families. Herein, key established biomarkers and prognostic scoring ... ...

Abstract	Prognostic imaging biomarkers after acute brain injury inform treatment decisions, track the progression of intracranial injury, and can be used in shared decision-making processes with families. Herein, key established biomarkers and prognostic scoring systems are surveyed in the literature, and their applications in clinical practice and clinical trials are discussed. Biomarkers in acute ischemic stroke include computed tomography (CT) hypodensity scoring, diffusion-weighted lesion volume, and core infarct size on perfusion imaging. Intracerebral hemorrhage biomarkers include hemorrhage volume, expansion, and location. Aneurysmal subarachnoid biomarkers include hemorrhage grading, presence of diffusion-restricting lesions, and acute hydrocephalus. Traumatic brain injury CT scoring systems, contusion expansion, and diffuse axonal injury grading are reviewed. Emerging biomarkers including white matter disease scoring, diffusion tensor imaging, and the automated calculation of scoring systems and volumetrics are discussed.
MeSH term(s)	Humans ; Diffusion Tensor Imaging ; Magnetic Resonance Imaging/methods ; Prognosis ; Ischemic Stroke/pathology ; Brain Injuries ; Neuroimaging/methods ; Brain Injuries, Traumatic/diagnostic imaging ; Brain Injuries, Traumatic/pathology ; Cerebrovascular Trauma/pathology ; Hemorrhage/pathology ; Brain/pathology
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0043-1775790
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Prognostic Neuroimaging Biomarkers in Acute Vascular Brain Injury and Traumatic Brain Injury

Krawchuk, Lindsey J. / Sharrock, Matthew F.

Seminars in Neurology

(Neuroprognostication)

2023 Volume 43, Issue 05, Page(s) 699–711

Series title	Neuroprognostication
Abstract	Prognostic imaging biomarkers after acute brain injury inform treatment decisions, track the progression of intracranial injury, and can be used in shared decision-making processes with families. Herein, key established biomarkers and prognostic scoring systems are surveyed in the literature, and their applications in clinical practice and clinical trials are discussed. Biomarkers in acute ischemic stroke include computed tomography (CT) hypodensity scoring, diffusion-weighted lesion volume, and core infarct size on perfusion imaging. Intracerebral hemorrhage biomarkers include hemorrhage volume, expansion, and location. Aneurysmal subarachnoid biomarkers include hemorrhage grading, presence of diffusion-restricting lesions, and acute hydrocephalus. Traumatic brain injury CT scoring systems, contusion expansion, and diffuse axonal injury grading are reviewed. Emerging biomarkers including white matter disease scoring, diffusion tensor imaging, and the automated calculation of scoring systems and volumetrics are discussed.
Keywords	imaging ; brain injury ; outcome ; prognostication ; neuroimaging ; computed tomography ; magnetic resonance imaging
Language	English
Publishing date	2023-10-01
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0043-1775790
Database	Thieme publisher's database

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Zs.A 1737: Show issues

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Article ; Online: Bayesian deep learning outperforms clinical trial estimators of intracerebral and intraventricular hemorrhage volume.

Sharrock, Matthew F / Mould, W Andrew / Hildreth, Meghan / Ryu, E Paul / Walborn, Nathan / Awad, Issam A / Hanley, Daniel F / Muschelli, John

Journal of neuroimaging : official journal of the American Society of Neuroimaging

2022 Volume 32, Issue 5, Page(s) 968–976

Abstract: Background and purpose: Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) clinical trials rely on manual linear and semi-quantitative (LSQ) estimators like the ABC/2, modified Graeb and IVH scores for timely volumetric estimation from ...

Abstract	Background and purpose: Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) clinical trials rely on manual linear and semi-quantitative (LSQ) estimators like the ABC/2, modified Graeb and IVH scores for timely volumetric estimation from CT. Deep learning (DL) volumetrics of ICH have recently approached the accuracy of gold-standard planimetry. However, DL and LSQ strategies have been limited by unquantified uncertainty, in particular when ICH and IVH estimates intersect. Bayesian deep learning methods can be used to approximate uncertainty, presenting an opportunity to improve quality assurance in clinical trials. Methods: A DL model was trained to simultaneously segment ICH and IVH using diagnostic CT data from the Minimally Invasive Surgery Plus Alteplase for ICH Evacuation (MISTIE) III and Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR) III clinical trials. Bayesian uncertainty approximation was performed using Monte-Carlo dropout. We compared the performance of our model with estimators used in the CLEAR IVH and MISTIE II trials. The reliability of planimetry, DL, and LSQ volumetrics in the setting of high ICH and IVH intersection is quantified using consensus estimates. Results: Our DL model produced volume correlations and median Dice scores of .994 and .946 for ICH in MISTIE II, and .980 and .863 for IVH in CLEAR IVH, respectively, outperforming LSQ estimates from the clinical trials. We found significant linear relationships between ICH uncertainty, Dice scores (r = -.849), and relative volume difference (r = .735). Conclusion: In our validation clinical trial dataset, DL models with Bayesian uncertainty approximation provided superior volumetric estimates to LSQ methods with real-time estimates of model uncertainty.
MeSH term(s)	Bayes Theorem ; Cerebral Hemorrhage/diagnostic imaging ; Cerebral Hemorrhage/surgery ; Clinical Trials as Topic ; Deep Learning ; Humans ; Reproducibility of Results ; Tissue Plasminogen Activator/therapeutic use
Chemical Substances	Tissue Plasminogen Activator (EC 3.4.21.68)
Language	English
Publishing date	2022-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1071724-9
ISSN	1552-6569 ; 1051-2284
ISSN (online)	1552-6569
ISSN	1051-2284
DOI	10.1111/jon.12997
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Zs.A 3211: Show issues

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Article ; Online: Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage.

Avadhani, Radhika / Ziai, Wendy C / Thompson, Richard E / Mould, W Andrew / Lane, Karen / Nanni, Angeline / Iacobelli, Michael / Sharrock, Matthew F / Sansing, Lauren H / Van Eldik, Linda J / Hanley, Daniel F

Neurocritical care

2023 Volume 40, Issue 2, Page(s) 807–815

Abstract: Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute ... ...

Abstract	Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a "worst-case" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.
MeSH term(s)	Adult ; Humans ; Brain Edema/etiology ; Brain Edema/complications ; Neuroinflammatory Diseases ; Cerebral Hemorrhage/complications ; Edema/complications ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Piperazines ; Pyridazines ; Pyridines
Chemical Substances	TT-301 (CY416F5NSK) ; Piperazines ; Pyridazines ; Pyridines
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2381896-7
ISSN	1556-0961 ; 1541-6933
ISSN (online)	1556-0961
ISSN	1541-6933
DOI	10.1007/s12028-023-01867-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 6538: Show issues

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Article ; Online: 3D Deep Neural Network Segmentation of Intracerebral Hemorrhage: Development and Validation for Clinical Trials.

Sharrock, Matthew F / Mould, W Andrew / Ali, Hasan / Hildreth, Meghan / Awad, Issam A / Hanley, Daniel F / Muschelli, John

Neuroinformatics

2020 Volume 19, Issue 3, Page(s) 403–415

Abstract: Intracranial hemorrhage (ICH) occurs when a blood vessel ruptures in the brain. This leads to significant morbidity and mortality, the likelihood of which is predicated on the size of the bleeding event. X-ray computed tomography (CT) scans allow ... ...

Abstract	Intracranial hemorrhage (ICH) occurs when a blood vessel ruptures in the brain. This leads to significant morbidity and mortality, the likelihood of which is predicated on the size of the bleeding event. X-ray computed tomography (CT) scans allow clinicians and researchers to qualitatively and quantitatively diagnose hemorrhagic stroke, guide interventions and determine inclusion criteria of patients in clinical trials. There is no currently available open source, validated tool to quickly segment hemorrhage. Using an automated pipeline and 2D and 3D deep neural networks, we show that we can quickly and accurately estimate ICH volume with high agreement with time-consuming manual segmentation. The training and validation datasets include significant heterogeneity in terms of pathology, such as the presence of intraventricular (IVH) or subdural hemorrhages (SDH) as well as variable image acquisition parameters. We show that deep neural networks trained with an appropriate anatomic context in the network receptive field, can effectively perform ICH segmentation, but those without enough context will overestimate hemorrhage along the skull and around calcifications in the ventricular system. We trained with all data from a multi-center phase II study (n = 112) achieving a best mean and median Dice coefficient of 0.914 and 0.919, a volume correlation of 0.979 and an average volume difference of 1.7 ml and root mean squared error of 4.7 ml in 500 out-of-sample scans from the corresponding multi-center phase III study. 3D networks with appropriate anatomic context outperformed both 2D and random forest models. Our results suggest that deep neural network models, when carefully developed can be incorporated into the workflow of an ICH clinical trial series to quickly and accurately segment ICH, estimate total hemorrhage volume and minimize segmentation failures. The model, weights and scripts for deployment are located at https://github.com/msharrock/deepbleed . This is the first publicly available neural network model for segmentation of ICH, the only model evaluated with the presence of both IVH and SDH and the only model validated in the workflow of a series of clinical trials.
MeSH term(s)	Brain ; Cerebral Hemorrhage/diagnostic imaging ; Humans ; Image Processing, Computer-Assisted ; Neural Networks, Computer ; Skull ; Tomography, X-Ray Computed
Language	English
Publishing date	2020-09-27
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2111941-7
ISSN	1559-0089 ; 1539-2791
ISSN (online)	1559-0089
ISSN	1539-2791
DOI	10.1007/s12021-020-09493-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5816: Show issues

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Article ; Online: Percutaneous balloon rhizotomy for trigeminal neuralgia using three-dimensional fluoroscopy.

Olivero, William C / Wang, Huan / Rak, Richard / Sharrock, Matthew F

World neurosurgery

2012 Volume 77, Issue 1, Page(s) 202.e1–3

Abstract: Background: Percutaneous balloon rhizotomy is one of the standard techniques for the treatment of trigeminal neuralgia. However, there have been well-reported complications from cannulating the foramen ovale (FO). We describe a novel technique for ... ...

Abstract	Background: Percutaneous balloon rhizotomy is one of the standard techniques for the treatment of trigeminal neuralgia. However, there have been well-reported complications from cannulating the foramen ovale (FO). We describe a novel technique for cannulating the FO using 3-dimensional (3D) rotational fluoroscopy. Methods: Three-dimensional rotational fluoroscopy is used to reconstruct the skull base. The optimal working projection is thus generated to best visualize the FO. When the optimal working projection is not anatomically feasible, for example, in a patient with severe cervical spondylosis, further rotational fluoroscopic data acquisition can assess the position of the needle to determine its relationship to the foramen. Furthermore, while inflated, the balloon position can also be verified with the same rotational technique. Results: Three-dimensional rotational fluoroscopy allows quick, safe, and easy cannulation of the FO. The equipment is readily available in the biplanar fluoroscopy suite. Its use should decrease the incidence of complications reported with the standard fluoroscopic technique. Conclusions: Three-dimensional rotational fluoroscopy allows real-time visual guidance to cannulate the FO and determine the optimal position of the inflated balloon. We believe that this is an important adjunct for treating trigeminal neuralgia via percutaneous techniques.
MeSH term(s)	Aged ; Catheterization ; Dementia/complications ; Female ; Fluoroscopy/methods ; Foramen Ovale/diagnostic imaging ; Foramen Ovale/surgery ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; Neurosurgical Procedures/methods ; Recurrence ; Rhizotomy/methods ; Skull Base/diagnostic imaging ; Skull Base/surgery ; Spondylosis/complications ; Spondylosis/surgery ; Surgery, Computer-Assisted/methods ; Trigeminal Neuralgia/surgery
Language	English
Publishing date	2012-01
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2011.03.041
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Brain temperature and its fundamental properties: a review for clinical neuroscientists.

Wang, Huan / Wang, Bonnie / Normoyle, Kieran P / Jackson, Kevin / Spitler, Kevin / Sharrock, Matthew F / Miller, Claire M / Best, Catherine / Llano, Daniel / Du, Rose

Frontiers in neuroscience

2014 Volume 8, Page(s) 307

Abstract: Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature ... ...

Abstract	Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically "expensive" organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective.
Language	English
Publishing date	2014-10-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2014.00307
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Omega-3 fatty acids as a putative treatment for traumatic brain injury.

Hasadsri, Linda / Wang, Bonnie H / Lee, James V / Erdman, John W / Llano, Daniel A / Barbey, Aron K / Wszalek, Tracey / Sharrock, Matthew F / Wang, Huan John

Journal of neurotrauma

2013 Volume 30, Issue 11, Page(s) 897–906

Abstract: Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, ... ...

Abstract	Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the "signature injury" in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo, and how this may be a particularly promising approach to improving functional outcome in patients with TBI.
MeSH term(s)	Animals ; Brain Injuries/diet therapy ; Dietary Supplements ; Fatty Acids, Omega-3/administration & dosage ; Humans
Chemical Substances	Fatty Acids, Omega-3
Language	English
Publishing date	2013-06-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2012.2672
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