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Article: Proton MR Spectroscopy of Pediatric Brain Disorders.

Blüml, Stefan / Saunders, Alexander / Tamrazi, Benita

2022 Volume 12, Issue 6

Abstract: In vivo MR spectroscopy is a non -invasive methodology that provides information about the biochemistry of tissues. It is available as a "push-button" application on state-of-the-art clinical MR scanners. MR spectroscopy has been used to study various ... ...

Abstract	In vivo MR spectroscopy is a non -invasive methodology that provides information about the biochemistry of tissues. It is available as a "push-button" application on state-of-the-art clinical MR scanners. MR spectroscopy has been used to study various brain diseases including tumors, stroke, trauma, degenerative disorders, epilepsy/seizures, inborn errors, neuropsychiatric disorders, and others. The purpose of this review is to provide an overview of MR spectroscopy findings in the pediatric population and its clinical use.
Language	English
Publishing date	2022-06-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12061462
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Article: Advanced Techniques and Applications in Magnetic Resonance Spectroscopy for Pediatric Patients

Tamrazi, Benita

Journal of Pediatric Neurology

(Advanced Approaches to Pediatric Neuroimaging)

2017 Volume 16, Issue 02, Page(s) 94–105

Abstract: Magnetic resonance spectroscopy (MRS) is a noninvasive tool that is often used in conjunction with conventional MR imaging to acquire information regarding the biochemistry of tissue. In pediatric patients, the traditional clinical application of MRS was ...

Series title	Advanced Approaches to Pediatric Neuroimaging
Abstract	Magnetic resonance spectroscopy (MRS) is a noninvasive tool that is often used in conjunction with conventional MR imaging to acquire information regarding the biochemistry of tissue. In pediatric patients, the traditional clinical application of MRS was in the preoperative diagnostic workup of brain tumors. In recent years with the boom of molecular testing, MRS application for tumor evaluation is becoming more advanced, now potentially serving as a biomarker for molecular subgroup classification. This article will review MRS techniques as well as clinical applications, both conventional and more advanced applications in the pediatric population including tumor assessment, hypoxic-ischemic injury, abusive head injury, and autism.
Keywords	MR spectroscopy ; pediatric brain tumors ; hypoxic-ischemic encephalopathy ; abusive head injury ; autism
Language	English
Publishing date	2017-07-19
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ISSN	1875-9041 ; 1304-2580
ISSN (online)	1875-9041
ISSN	1304-2580
DOI	10.1055/s-0037-1604217
Database	Thieme publisher's database

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Article ; Online: Neuroimaging of complications arising after CD19 chimeric antigen receptor T-cell therapy: A review.

Pinto, Soniya N / Liu, Chia-Shang J / Nelson, Marvin D / Bluml, Stefan / Livingston, David / Tamrazi, Benita

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

2023 Volume 33, Issue 5, Page(s) 703–715

Abstract: Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR ...

Abstract	Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Receptors, Chimeric Antigen ; Posterior Leukoencephalopathy Syndrome ; Neuroimaging ; Antigens, CD19/adverse effects ; Cell- and Tissue-Based Therapy
Chemical Substances	Receptors, Chimeric Antigen ; cell-associated neurotoxicity ; Antigens, CD19
Language	English
Publishing date	2023-06-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1071724-9
ISSN	1552-6569 ; 1051-2284
ISSN (online)	1552-6569
ISSN	1051-2284
DOI	10.1111/jon.13138
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Article ; Online: Increasing Cervical Kyphosis Correlates With Cervical Degenerative Disk Disease in Patients With Adolescent Idiopathic Scoliosis.

Lin, Adrian / Skaggs, David L / Andras, Lindsay M / Tolo, Vernon / Tamrazi, Benita / Illingworth, Kenneth D

Spine

2023 Volume 49, Issue 7, Page(s) 486–491

Abstract: Study design: Retrospective review.: Objective: Our goal was to investigate the incidence of cervical degenerative disk disease (DDD) in patients with adolescent idiopathic scoliosis (AIS), before surgical intervention.: Summary of background data!# ...

Abstract	Study design: Retrospective review. Objective: Our goal was to investigate the incidence of cervical degenerative disk disease (DDD) in patients with adolescent idiopathic scoliosis (AIS), before surgical intervention. Summary of background data: AIS is often associated with thoracic hypokyphosis and compensatory cervical kyphosis. In adults, cervical kyphosis is associated with DDD. Although cervical kyphosis has been reported in up to 60% AIS patients, the association with cervical DDD has not been reported. Materials and methods: A retrospective review was conducted from January 2014 to December 2019 of all consecutive AIS patients. Inclusion criteria were AIS patients over 10 years of age with cervical magnetic resonance imaging and anterior-posterior and lateral spine radiographs within 1 year of each other. Magnetic resonance imaging were reviewed for evidence of cervical DDD. Severity of cervical changes were graded using the Pfirrmann classification and by a quantitative measure of disk degeneration, the magnetic resonance signal intensity ratio. Results: Eighty consecutive patients were included (mean age: 14.1 years, SD=2.5 years). Increasing cervical kyphosis was significantly correlated to decreasing thoracic kyphosis ( r =0.49, P <0.01) and increasing major curve magnitude ( r =0.22, P =0.04). Forty-five patients (56%) had the presence of DDD (grades 2-4) with a mean cervical kyphosis of 11.1° (SD=9.5°, P <0.01). More cervical kyphosis was associated with more severe cervical DDD as graded by Pfirrmann classification level ( P <0.01). Increasing cervical kyphosis was also positively associated with increasing magnetic resonance signal intensity ratio ( P <0.01). Nine patients had ventral cord effacement secondary to DDD with a mean cervical kyphosis of 22.8° (SD=8.6°) compared with 2.6° (SD=11.2°) in those who did not ( P <0.01). Conclusions: Cervical kyphosis was significantly associated with increasing severity of cervical DDD in patients with AIS. Patients with evidence of ventral cord effacement had the largest degree of cervical kyphosis with a mean of 22.8±8.6°. This is the first study to evaluate the association between cervical kyphosis in AIS with cervical DDD.
MeSH term(s)	Adult ; Humans ; Adolescent ; Scoliosis/diagnostic imaging ; Scoliosis/epidemiology ; Scoliosis/surgery ; Intervertebral Disc Degeneration/diagnostic imaging ; Intervertebral Disc Degeneration/epidemiology ; Thoracic Vertebrae/diagnostic imaging ; Thoracic Vertebrae/surgery ; Lumbar Vertebrae/surgery ; Kyphosis/diagnostic imaging ; Kyphosis/epidemiology ; Kyphosis/surgery ; Retrospective Studies ; Spinal Fusion/methods
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	752024-4
ISSN	1528-1159 ; 0362-2436
ISSN (online)	1528-1159
ISSN	0362-2436
DOI	10.1097/BRS.0000000000004824
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Article ; Online: Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia.

Tetarbe, Manas / Wisnowski, Jessica L / Geyer, Eduardo / Tamrazi, Benita / Wood, Thomas / Mietzsch, Ulrike / Blüml, Stefan / Wu, Tai-Wei

The Journal of pediatrics

2023 Volume 261, Page(s) 113560

Abstract: Objective: To determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH).: Methods: This was an observational study in ... ...

Abstract	Objective: To determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH). Methods: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. Results: Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern. Conclusions: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.
MeSH term(s)	Infant, Newborn ; Infant ; Humans ; Female ; Hypoxia-Ischemia, Brain/therapy ; Hypoxia-Ischemia, Brain/pathology ; Blood Glucose ; Hypothermia, Induced/adverse effects ; Hypothermia, Induced/methods ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Spectroscopy
Chemical Substances	Blood Glucose
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2023.113560
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Article ; Online: m.3685T > C is a novel mitochondrial DNA variant that causes Leigh syndrome.

Jean, Jeffrey / Christodoulou, Eirini / Gai, Xiaowu / Tamrazi, Benita / Vera, Moin / Mitchell, Wendy G / Schmidt, Ryan J

Cold Spring Harbor molecular case studies

2022 Volume 8, Issue 2

Abstract: Variants in the mitochondrial genome can result in dysfunction of Complex I within the electron transport chain, thus causing disruptions in oxidative phosphorylation. Pathogenic variants in ... ...

Abstract	Variants in the mitochondrial genome can result in dysfunction of Complex I within the electron transport chain, thus causing disruptions in oxidative phosphorylation. Pathogenic variants in the
MeSH term(s)	DNA, Mitochondrial/genetics ; Female ; Humans ; Lactic Acid ; Leigh Disease/genetics ; Mitochondrial Diseases/genetics ; Mutation ; Seizures
Chemical Substances	DNA, Mitochondrial ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2835759-0
ISSN	2373-2873 ; 2373-2873
ISSN (online)	2373-2873
ISSN	2373-2873
DOI	10.1101/mcs.a006136
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Article: Quantitative Nuclear Histomorphometry Predicts Molecular Subtype and Clinical Outcome in Medulloblastomas: Preliminary Findings.

Whitney, Jon / Dollinger, Liisa / Tamrazi, Benita / Hawes, Debra / Couce, Marta / Marcheque, Julia / Judkins, Alexander / Margol, Ashley / Madabhushi, Anant

Journal of pathology informatics

2022 Volume 13, Page(s) 100090

Abstract: Molecular subtypes of medulloblastoma [Sonic Hedgehog (SHH), Wingless/INT (WNT), Group 3, and Group 4] are defined by common patterns of gene expression. These differential gene expression patterns appear to result in different histomorphology and ... ...

Abstract	Molecular subtypes of medulloblastoma [Sonic Hedgehog (SHH), Wingless/INT (WNT), Group 3, and Group 4] are defined by common patterns of gene expression. These differential gene expression patterns appear to result in different histomorphology and prognosis. Quantitative histomorphometry is a well-known method of computer-aided pathology image analysis. The hypotheses we sought to examine in this preliminary proof of concept study were whether computer extracted nuclear morphological features of medulloblastomas from digitized tissue slide images could independently: (1) distinguish between molecularly determined subgroups and (2) identify patterns within these subgroups that correspond with clinical outcome. Our dataset was composed of 46 medulloblastoma patients: 16 SHH (5 dead, 11 survived), 3 WNT (0 dead, 3 survived), 12 Group 3 (4 dead, 8 survived), and 15 were Group 4 (5 dead, 10 survived). A watershed-based thresholding scheme was used to automatically identify individual nuclei within digitized whole slide hematoxylin and eosin tissue images. Quantitative histomorphometric features corresponding to the texture (variation in pixel intensity), shape (variations in size, roundness), and architectural rearrangement (distances between, and number of connected neighbors) of nuclei were subsequently extracted. These features were ranked using feature selection schemes and these top-ranked features were then used to train machine-learning classifiers via threefold cross-validation to separate patients based on: (1) molecular subtype and (2) disease-specific outcomes within the individual molecular subtype groups. SHH and WNT tumors were separated from Groups 3 and 4 tumors with a maximum area under the receiver operating characteristic curve (AUC) of 0.7, survival within Group 3 tumors was predicted with an AUC of 0.92, and Group 3 and 4 patients were separated into high- and low-risk groups with
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2579241-6
ISSN	2153-3539 ; 2229-5089
ISSN (online)	2153-3539
ISSN	2229-5089
DOI	10.1016/j.jpi.2022.100090
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Article: Quantitative Susceptibility Mapping: Translating an Investigative Research Tool into High Volume Clinical Diagnostic Imaging.

Borzage, Matthew T / Doyle, Eamon K / Liu, Chia-Shang J / Nelson, Marvin D / Blüml, Stefan / Wood, John C / Tamrazi, Benita

Diagnostics (Basel, Switzerland)

2022 Volume 12, Issue 12

Abstract: Quantitative susceptibility mapping (QSM) is an MRI-based technique for iron quantification of targeted tissue. QSM provides information relevant to clinicians in a broad range of diagnostic contexts, including sickle cell disease, inflammatory/ ... ...

Abstract	Quantitative susceptibility mapping (QSM) is an MRI-based technique for iron quantification of targeted tissue. QSM provides information relevant to clinicians in a broad range of diagnostic contexts, including sickle cell disease, inflammatory/demyelinating processes, and neoplasms. However, major MRI vendors do not offer QSM post-processing in a form ready for general use. This work describes a vendor-agnostic approach for scaling QSM analysis from a research technique to a routine diagnostic test. We provide the details needed to seamlessly integrate hardware, software, and clinical systems to provide QSM processing for a busy clinical radiology workflow. This approach can be generalized to other advanced MRI acquisitions and analyses with proven diagnostic utility, yet without crucial MR vendor support.
Language	English
Publishing date	2022-11-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12122962
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Article ; Online: Addendum: Sustained response of three pediatric BRAFV600E mutated high-grade gliomas to combined BRAF and MEK inhibitor therapy.

Toll, Stephanie A / Tran, Hung N / Cotter, Jennifer / Judkins, Alexander R / Tamrazi, Benita / Biegel, Jaclyn A / Dhall, Girish / Robison, Nathan J / Waters, Kaaren / Patel, Palak / Cooper, Robert / Margol, Ashley S

Oncotarget

2023 Volume 14, Page(s) 502

Language	English
Publishing date	2023-05-19
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.28445
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Article ; Online: Pineal Region Masses in Pediatric Patients.

Tamrazi, Benita / Nelson, Marvin / Blüml, Stefan

Neuroimaging clinics of North America

2017 Volume 27, Issue 1, Page(s) 85–97

Abstract: A review of pediatric pineal region tumors is provided with emphasis on advanced imaging techniques. The 3 major categories of pineal region tumors include germ cell tumors, pineal parenchymal tumors, and tumors arising from adjacent structures such as ... ...

Abstract	A review of pediatric pineal region tumors is provided with emphasis on advanced imaging techniques. The 3 major categories of pineal region tumors include germ cell tumors, pineal parenchymal tumors, and tumors arising from adjacent structures such as tectal astrocytomas. The clinical presentation, biochemical markers, and imaging of these types of tumors are reviewed.
MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Child ; Diffusion Magnetic Resonance Imaging/methods ; Humans ; Magnetic Resonance Spectroscopy/methods ; Neuroimaging/methods ; Pineal Gland/diagnostic imaging
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1314594-0
ISSN	1557-9867 ; 1052-5149
ISSN (online)	1557-9867
ISSN	1052-5149
DOI	10.1016/j.nic.2016.08.002
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