Doris Lin - Academia.edu (original) (raw)

Papers by Doris Lin

Research paper thumbnail of NIMG-55. A Quantitative Analysis of Brain Volume Dynamics in PCNSL Patients Treated with High-Dose Methotrexate-Based Therapy

Neuro-oncology, Nov 1, 2020

NEURO-ONCOLOGY • NOVEMBER 2020 tients received surgery alone or followed by temozolomide chemothe... more NEURO-ONCOLOGY • NOVEMBER 2020 tients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS: At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS: The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).

Research paper thumbnail of Dynamic MR perfusion and proton MR spectroscopic imaging in sturge-weber syndrome: Correlation with neurological symptoms

Journal of Magnetic Resonance Imaging, 2006

Purpose: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusi... more Purpose: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status. Materials and Methods: Six consecutive patients with a clinically established diagnosis of SWS underwent MRI using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans, dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the neurological scores, and the imaging results were correlated with neurological scores using nonparametric correlation analysis. Results: Two patients had classic neuroimaging findings of unilateral cerebral atrophy with corresponding leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two patients had bilateral disease, and two had normal symmetric perfusion. Among clinical measures, the highest correlation was between hemiparesis index and hypoperfused tissue volume (Spearman's correlation coefficient, ϭ 0.943, P Ͻ 0.05). There was also a trend of correlation, although not statistically significant (P ϭ 0.06), between the hemiparesis score and the NAA/Cr ratio in the mid to posterior centrum semiovale, lateral gray matter (GM), and splenium. Conclusion: In SWS, PWI indicates cerebral hypoperfusion predominantly due to impaired venous drainage, with only the most severely affected regions in some patients also showing arterial perfusion deficiency. The extent and severity of the perfusion abnormality and neuronal loss/dysfunction reflect the severity of neurological symptoms and disability, and the highest correlation is found with the degree of hemiparesis. These parameters may be useful as quantitative measures of disease burden; however, further studies in larger number of patients (and with a more homogeneous age range) are required to confirm the preliminary findings reported here.

Research paper thumbnail of NIMG-97. Echo-Planar MR Spectroscopic Imaging in High Grade Glioma: Effect of Radiotherapy Treatment (RT)

Neuro-oncology, Nov 1, 2017

Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyo... more Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyond the solid tumor mass, invariably affecting the non-lesional hemisphere. In contrast, patients suffering from LGGs showed less damage to functional connectivity, which was mostly confined to the lesion-bearing hemisphere. In general, the degree of damage to functional connectivity was likely dominated by tumor histology, e.g. HGGs caused far more extensive damage to functional connectivity than LGGs. CONCLUSION: rsfMRI is a novel, non-invasive and easily implementable diagnostic tool in glioma patients which could discover characteristic disturbances in the non-lesional hemisphere of HGG patients. The correlation with tumor grading suggests that rsfMRI has great potential serve as an imaging biomarker for disease burden in glioma patients.

Research paper thumbnail of Distinguishing True Progression From Radionecrosis After Stereotactic Radiation Therapy for Brain Metastases With Machine Learning and Radiomics

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases... more Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases is a common phenomenon often indistinguishable from true progression. Radiomics is an emerging field that promises to improve on conventional imaging. In this study, we sought to apply a radiomics-based prediction model to the problem of diagnosing treatment effect after SRS. Methods and Materials: We included patients in the Johns Hopkins Health System who were treated with SRS for brain metastases who subsequently underwent resection for symptomatic growth. We also included cases of likely treatment effect in which lesions grew but subsequently regressed spontaneously. Lesions were segmented semiautomatically on preoperative T1 postcontrast and T2 fluid-attenuated inversion recovery magnetic resonance imaging, and radiomic features were extracted with software developed in-house. Top-performing features on univariate

Research paper thumbnail of Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI

npj Digital Medicine

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention a... more Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO2 fluctuations as a natural “contrast media”. The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO2-inhalation MRI, which includes data from young and older healthy subjects and patien...

Research paper thumbnail of Study protocol: retrospectively mining multisite clinical data to presymptomatically predict seizure onset for individual patients with Sturge-Weber

BMJ Open

IntroductionSecondary analysis of hospital-hosted clinical data can save time and cost compared w... more IntroductionSecondary analysis of hospital-hosted clinical data can save time and cost compared with prospective clinical trials for neuroimaging biomarker development. We present such a study for Sturge-Weber syndrome (SWS), a rare neurovascular disorder that affects 1 in 20 000–50 000 newborns. Children with SWS are at risk for developing neurocognitive deficit by school age. A critical period for early intervention is before 2 years of age, but early diagnostic and prognostic biomarkers are lacking. We aim to retrospectively mine clinical data for SWS at two national centres to develop presymptomatic biomarkers.Methods and analysisWe will retrospectively collect clinical, MRI and neurocognitive outcome data for patients with SWS who underwent brain MRI before 2 years of age at two national SWS care centres. Expert review of clinical records and MRI quality control will be used to refine the cohort. The merged multisite data will be used to develop algorithms for abnormality detec...

Research paper thumbnail of Quantification metrics for telangiectasia using optical coherence tomography

Scientific Reports, 2022

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascula... more Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)—a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion...

Research paper thumbnail of Perfusion measurement in brain gliomas using velocity-selective arterial spin labeling: comparison with pseudo-continuous arterial spin labeling and dynamic susceptibility contrast MRI

European Radiology, 2022

To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas ... more To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas by comparing with both pseudo-continuous (PC) ASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). Forty-four consecutive patients with newly diagnosed glioma who underwent preoperative perfusion MRI including VSASL, PCASL, and DSC-PWI between 2017 and 2019 were retrospectively evaluated. Visual inspection was performed to evaluate the tumor signal intensity relative to gray matter based on 1–5 score criteria and weighted kappa was used to evaluate the pair-wise concordance between VSASL or PCASL and DSC-PWI. The relative tumor blood flow (rTBF) was measured from sampling intra-tumoral areas of hot-spot on the blood flow map and normalized against the contralateral normal gray matter blood flow. Linear regression and Bland–Altman analyses were performed to evaluate the correlation and agreement of rTBF measurements between ASL methods and DSC-PWI. The ROC analysis was constructed to determine the diagnostic performance of three perfusion methods for grading gliomas. TBF maps derived from VSASL were more comparable with DSC-PWI than PCASL on visual inspection (weighted kappa of 0.90 vs 0.68). In quantitative analysis, VSASL-rTBF yielded higher correlation with the values from DSC-PWI than PCASL-rTBF (R2 = 80% vs 47%, p < 0.001 for both). Both ASL and DSC-derived rTBF showed good distinction between low-grade and high-grade gliomas (p < 0.001). Compared to PCASL, VSASL yielded superior diagnostic sensitivity, specificity, and accuracy in glioma grading. VSASL showed great promise for accurate quantification of TBF and could potentially improve the diagnostic performance of ASL in preoperative grading of gliomas. • VSASL demonstrated a greater agreement with DSC-PWI than with PCASL on visual inspection and perfusion quantification. • VSASL showed a higher diagnostic sensitivity, negative predictive value, and accuracy than PCASL for glioma grading. • With the advantages of insensitivity to transit delay and no need of prescribing a labeling plane, VSASL could potentially improve the diagnostic performance of ASL for a more accurate, noninvasive quantification of TBF in patients with glioma.

Research paper thumbnail of Dose‐Lowering in Contrast‐Enhanced MRI of the Central Nervous System: A Retrospective, Parallel‐Group Comparison Using Gadobenate Dimeglumine

Journal of Magnetic Resonance Imaging, 2021

BackgroundConcerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, l... more BackgroundConcerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols.PurposeTo compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS).Study TypeRetrospective, multicenter.PopulationThree hundred and fifty‐two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate.Field Strength/Sequences1.5 T and 3.0 T/precontrast and postcontrast T1‐weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2‐weighted FSE and T2‐FLAIR.AssessmentImages of patients with extra‐axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quanti...

Research paper thumbnail of Lesion evolution and neurodegeneration in RVCL-S

Neurology, 2020

ObjectiveTo characterize lesion evolution and neurodegeneration in retinal vasculopathy with cere... more ObjectiveTo characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI.MethodsWe prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically.ResultsTwenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL–S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = −0.908,...

Research paper thumbnail of MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI

NMR in Biomedicine, 2019

MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple ... more MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improveme...

Research paper thumbnail of Cerebral blood volume mapping using Fourier‐transform–based velocity‐selective saturation pulse trains

Magnetic Resonance in Medicine, 2019

PurposeVelocity‐selective saturation (VSS) pulse trains provide a viable alternative to the spati... more PurposeVelocity‐selective saturation (VSS) pulse trains provide a viable alternative to the spatially selective methods for measuring cerebral blood volume (CBV) by reducing the sensitivity to arterial transit time. This study is to compare the Fourier‐transform–based velocity‐selective saturation (FT‐VSS) pulse trains with the conventional flow‐dephasing VSS techniques for CBV quantification.MethodsThe proposed FT‐VSS label and control modules were compared with VSS pulse trains utilizing double refocused hyperbolic tangent (DRHT) and 8‐segment B1‐insensitive rotation (BIR‐8). This was done using both numerical simulations and phantom studies to evaluate their sensitivities to gradient imperfections such as eddy currents. DRHT, BIR‐8, and FT‐VSS prepared CBV mapping was further compared for velocity‐encoding gradients along 3 orthogonal directions in healthy subjects at 3T.ResultsThe phantom studies exhibited more consistent immunity to gradient imperfections for the utilized FT‐VS...

Research paper thumbnail of Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research

Pediatric Neurology, 2016

Research paper thumbnail of Hemorrhage Rates From Brain Arteriovenous Malformation in Patients With Hereditary Hemorrhagic Telangiectasia

Stroke; a journal of cerebral circulation, Jan 9, 2015

Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous ... more Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs). We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis. The majority of patients were women (58%) and white (98%). The mean age at BAVM diagnosis was 31±19 years (range, 0-70), with 61% of cases diagnosed on asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42-2.44%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher ...

Research paper thumbnail of Proton MR Spectroscopy in the Diagnostic Evaluation of Suspected Mitochondrial Disease in Iran

Iranian journal of child neurology, 2013

Mitochondrial diseases are a group of inherited disorders Caused by a derangement of mitochondria... more Mitochondrial diseases are a group of inherited disorders Caused by a derangement of mitochondrial respiration. The clinical manifestations are heterogeneous, and the diagnosis is often based on information acquired from multiple levels of inquiry that require a variety of diagnostic tests for proper determination. Neuroimaging may play a significant role in diagnosis. The various modalities of nuclear magnetic resonance imaging (MRI) allow for multiple independent detection procedures that can give important anatomical and metabolic clues for diagnosis when the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. The non-invasive nature of neuroimaging also allows for longitudinal studies. To date, no pathognomonic correlation between specific genetic defect and neuroimaging findings have been described. The de...

Research paper thumbnail of ATIM-06. A pilot Study of Stereotactic Radiosurgery (SRS) Combined with Ipilimumab Prolonged Survival in Patients with Newly Diagnosed Melanoma Brain Metastases

Neuro-Oncology, 2017

NEURO-ONCOLOGY • NOVEMBER 2017 include overall survival, development of brain metastases, neuroco... more NEURO-ONCOLOGY • NOVEMBER 2017 include overall survival, development of brain metastases, neurocognitive function, and QOL outcomes. TRIAL DESIGN: This is a prospective, singlearm, open-label multicenter pilot study. All patients will undergo TTFields treatment using the NovoTTF-200A System set to an output frequency of 200 kHz. The feasibility of TTFields prophylaxis will be measured as the percentage of patients continuing TTFields therapy until intracranial tumor progression, discontinuation due to disease limiting toxicity, or continuation of therapy for at least 6 months. TTFields will be discontinued in patients who develop intracranial failure while on therapy. All patients who develop intracranial failure may undergo whole brain radiotherapy or best supportive care at the discretion of the treating physician. All study follow-up procedures are to continue according to protocol until death, or until another criteria for removal is met. Because the primary endpoint is feasibility, the proposed sample size is not driven by statistical hypotheses. A sample size of 25 was set to accumulate more extensive patient data for planning the next clinical phase of this potential prophylactic treatment.

Research paper thumbnail of NIMG-97. Echo-Planar MR Spectroscopic Imaging in High Grade Glioma: Effect of Radiotherapy Treatment (RT)

Neuro-Oncology, 2017

Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyo... more Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyond the solid tumor mass, invariably affecting the non-lesional hemisphere. In contrast, patients suffering from LGGs showed less damage to functional connectivity, which was mostly confined to the lesion-bearing hemisphere. In general, the degree of damage to functional connectivity was likely dominated by tumor histology, e.g. HGGs caused far more extensive damage to functional connectivity than LGGs. CONCLUSION: rsfMRI is a novel, non-invasive and easily implementable diagnostic tool in glioma patients which could discover characteristic disturbances in the non-lesional hemisphere of HGG patients. The correlation with tumor grading suggests that rsfMRI has great potential serve as an imaging biomarker for disease burden in glioma patients.

Research paper thumbnail of Osteogenesis Imperfecta of the Temporal Bone 1

A 36-year-old African-American woman who had a history of fluctuating bilateral mixed hearing los... more A 36-year-old African-American woman who had a history of fluctuating bilateral mixed hearing loss that was worse on the left side than on the right complained of worsening of hearing on the right side during follow-up. At physical examination, she was a short obese woman who was wheelchair bound. The scleras were discolored. The tympanic membranes were intact. Audiogram findings demonstrated profound hearing loss on the left side and moderately severe mixed conductive and sensorineural hearing loss on the right side. In the past, she had fluctuations in her hearing with overall progressive deterioration; steroid treatment was unsuccessful. Unenhanced computed tomographic (CT) scans of the petrous temporal bones were obtained with a bone algorithm. Transverse scans of the right side (Fig 1a, 1b) and coronal scans (Fig 1c, 1d) of both sides were obtained.

Research paper thumbnail of Genotype–Phenotype Correlations in Children with HHT

Journal of Clinical Medicine, 2020

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by m... more Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presenc...

Research paper thumbnail of NIMG-55. A Quantitative Analysis of Brain Volume Dynamics in PCNSL Patients Treated with High-Dose Methotrexate-Based Therapy

Neuro-Oncology, 2020

BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (... more BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX. SUBJECTS/METHODS We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to c...

Research paper thumbnail of NIMG-55. A Quantitative Analysis of Brain Volume Dynamics in PCNSL Patients Treated with High-Dose Methotrexate-Based Therapy

Neuro-oncology, Nov 1, 2020

NEURO-ONCOLOGY • NOVEMBER 2020 tients received surgery alone or followed by temozolomide chemothe... more NEURO-ONCOLOGY • NOVEMBER 2020 tients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS: At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS: The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).

Research paper thumbnail of Dynamic MR perfusion and proton MR spectroscopic imaging in sturge-weber syndrome: Correlation with neurological symptoms

Journal of Magnetic Resonance Imaging, 2006

Purpose: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusi... more Purpose: To investigate physiological alterations in Sturge-Weber syndrome (SWS) using MR perfusion imaging (PWI) and proton spectroscopic imaging (MRSI), and their association with neurological status. Materials and Methods: Six consecutive patients with a clinically established diagnosis of SWS underwent MRI using a 1.5 Tesla scanner. The protocol consisted of conventional anatomic scans, dynamic PWI, and multislice MRSI. A pediatric neurologist evaluated the neurological scores, and the imaging results were correlated with neurological scores using nonparametric correlation analysis. Results: Two patients had classic neuroimaging findings of unilateral cerebral atrophy with corresponding leptomeningeal enhancement and hypoperfusion (prolonged mean transit time). Two patients had bilateral disease, and two had normal symmetric perfusion. Among clinical measures, the highest correlation was between hemiparesis index and hypoperfused tissue volume (Spearman's correlation coefficient, ϭ 0.943, P Ͻ 0.05). There was also a trend of correlation, although not statistically significant (P ϭ 0.06), between the hemiparesis score and the NAA/Cr ratio in the mid to posterior centrum semiovale, lateral gray matter (GM), and splenium. Conclusion: In SWS, PWI indicates cerebral hypoperfusion predominantly due to impaired venous drainage, with only the most severely affected regions in some patients also showing arterial perfusion deficiency. The extent and severity of the perfusion abnormality and neuronal loss/dysfunction reflect the severity of neurological symptoms and disability, and the highest correlation is found with the degree of hemiparesis. These parameters may be useful as quantitative measures of disease burden; however, further studies in larger number of patients (and with a more homogeneous age range) are required to confirm the preliminary findings reported here.

Research paper thumbnail of NIMG-97. Echo-Planar MR Spectroscopic Imaging in High Grade Glioma: Effect of Radiotherapy Treatment (RT)

Neuro-oncology, Nov 1, 2017

Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyo... more Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyond the solid tumor mass, invariably affecting the non-lesional hemisphere. In contrast, patients suffering from LGGs showed less damage to functional connectivity, which was mostly confined to the lesion-bearing hemisphere. In general, the degree of damage to functional connectivity was likely dominated by tumor histology, e.g. HGGs caused far more extensive damage to functional connectivity than LGGs. CONCLUSION: rsfMRI is a novel, non-invasive and easily implementable diagnostic tool in glioma patients which could discover characteristic disturbances in the non-lesional hemisphere of HGG patients. The correlation with tumor grading suggests that rsfMRI has great potential serve as an imaging biomarker for disease burden in glioma patients.

Research paper thumbnail of Distinguishing True Progression From Radionecrosis After Stereotactic Radiation Therapy for Brain Metastases With Machine Learning and Radiomics

International Journal of Radiation Oncology Biology Physics, Nov 1, 2018

Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases... more Treatment effect or radiation necrosis after stereotactic radiosurgery (SRS) for brain metastases is a common phenomenon often indistinguishable from true progression. Radiomics is an emerging field that promises to improve on conventional imaging. In this study, we sought to apply a radiomics-based prediction model to the problem of diagnosing treatment effect after SRS. Methods and Materials: We included patients in the Johns Hopkins Health System who were treated with SRS for brain metastases who subsequently underwent resection for symptomatic growth. We also included cases of likely treatment effect in which lesions grew but subsequently regressed spontaneously. Lesions were segmented semiautomatically on preoperative T1 postcontrast and T2 fluid-attenuated inversion recovery magnetic resonance imaging, and radiomic features were extracted with software developed in-house. Top-performing features on univariate

Research paper thumbnail of Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI

npj Digital Medicine

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention a... more Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO2 fluctuations as a natural “contrast media”. The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO2-inhalation MRI, which includes data from young and older healthy subjects and patien...

Research paper thumbnail of Study protocol: retrospectively mining multisite clinical data to presymptomatically predict seizure onset for individual patients with Sturge-Weber

BMJ Open

IntroductionSecondary analysis of hospital-hosted clinical data can save time and cost compared w... more IntroductionSecondary analysis of hospital-hosted clinical data can save time and cost compared with prospective clinical trials for neuroimaging biomarker development. We present such a study for Sturge-Weber syndrome (SWS), a rare neurovascular disorder that affects 1 in 20 000–50 000 newborns. Children with SWS are at risk for developing neurocognitive deficit by school age. A critical period for early intervention is before 2 years of age, but early diagnostic and prognostic biomarkers are lacking. We aim to retrospectively mine clinical data for SWS at two national centres to develop presymptomatic biomarkers.Methods and analysisWe will retrospectively collect clinical, MRI and neurocognitive outcome data for patients with SWS who underwent brain MRI before 2 years of age at two national SWS care centres. Expert review of clinical records and MRI quality control will be used to refine the cohort. The merged multisite data will be used to develop algorithms for abnormality detec...

Research paper thumbnail of Quantification metrics for telangiectasia using optical coherence tomography

Scientific Reports, 2022

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascula... more Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)—a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion...

Research paper thumbnail of Perfusion measurement in brain gliomas using velocity-selective arterial spin labeling: comparison with pseudo-continuous arterial spin labeling and dynamic susceptibility contrast MRI

European Radiology, 2022

To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas ... more To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas by comparing with both pseudo-continuous (PC) ASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). Forty-four consecutive patients with newly diagnosed glioma who underwent preoperative perfusion MRI including VSASL, PCASL, and DSC-PWI between 2017 and 2019 were retrospectively evaluated. Visual inspection was performed to evaluate the tumor signal intensity relative to gray matter based on 1–5 score criteria and weighted kappa was used to evaluate the pair-wise concordance between VSASL or PCASL and DSC-PWI. The relative tumor blood flow (rTBF) was measured from sampling intra-tumoral areas of hot-spot on the blood flow map and normalized against the contralateral normal gray matter blood flow. Linear regression and Bland–Altman analyses were performed to evaluate the correlation and agreement of rTBF measurements between ASL methods and DSC-PWI. The ROC analysis was constructed to determine the diagnostic performance of three perfusion methods for grading gliomas. TBF maps derived from VSASL were more comparable with DSC-PWI than PCASL on visual inspection (weighted kappa of 0.90 vs 0.68). In quantitative analysis, VSASL-rTBF yielded higher correlation with the values from DSC-PWI than PCASL-rTBF (R2 = 80% vs 47%, p < 0.001 for both). Both ASL and DSC-derived rTBF showed good distinction between low-grade and high-grade gliomas (p < 0.001). Compared to PCASL, VSASL yielded superior diagnostic sensitivity, specificity, and accuracy in glioma grading. VSASL showed great promise for accurate quantification of TBF and could potentially improve the diagnostic performance of ASL in preoperative grading of gliomas. • VSASL demonstrated a greater agreement with DSC-PWI than with PCASL on visual inspection and perfusion quantification. • VSASL showed a higher diagnostic sensitivity, negative predictive value, and accuracy than PCASL for glioma grading. • With the advantages of insensitivity to transit delay and no need of prescribing a labeling plane, VSASL could potentially improve the diagnostic performance of ASL for a more accurate, noninvasive quantification of TBF in patients with glioma.

Research paper thumbnail of Dose‐Lowering in Contrast‐Enhanced MRI of the Central Nervous System: A Retrospective, Parallel‐Group Comparison Using Gadobenate Dimeglumine

Journal of Magnetic Resonance Imaging, 2021

BackgroundConcerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, l... more BackgroundConcerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols.PurposeTo compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS).Study TypeRetrospective, multicenter.PopulationThree hundred and fifty‐two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate.Field Strength/Sequences1.5 T and 3.0 T/precontrast and postcontrast T1‐weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2‐weighted FSE and T2‐FLAIR.AssessmentImages of patients with extra‐axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quanti...

Research paper thumbnail of Lesion evolution and neurodegeneration in RVCL-S

Neurology, 2020

ObjectiveTo characterize lesion evolution and neurodegeneration in retinal vasculopathy with cere... more ObjectiveTo characterize lesion evolution and neurodegeneration in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) using multimodal MRI.MethodsWe prospectively performed MRI and cognitive testing in RVCL-S and healthy control cohorts. Gray and white matter volume and disruption of white matter microstructure were quantified. Asymmetric spin echo acquisition permitted voxel-wise oxygen extraction fraction (OEF) calculation as an in vivo marker of microvascular ischemia. The RVCL-S cohort was included in a longitudinal analysis of lesion subtypes in which hyperintense lesions on fluid-attenuated inversion recovery (FLAIR), T1-postgadolinium, and diffusion-weighted imaging were delineated and quantified volumetrically.ResultsTwenty individuals with RVCL-S and 26 controls were enrolled. White matter volume and microstructure declined faster in those with RVCL–S compared to controls. White matter atrophy in RVCL-S was highly linear (ρ = −0.908,...

Research paper thumbnail of MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI

NMR in Biomedicine, 2019

MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple ... more MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improveme...

Research paper thumbnail of Cerebral blood volume mapping using Fourier‐transform–based velocity‐selective saturation pulse trains

Magnetic Resonance in Medicine, 2019

PurposeVelocity‐selective saturation (VSS) pulse trains provide a viable alternative to the spati... more PurposeVelocity‐selective saturation (VSS) pulse trains provide a viable alternative to the spatially selective methods for measuring cerebral blood volume (CBV) by reducing the sensitivity to arterial transit time. This study is to compare the Fourier‐transform–based velocity‐selective saturation (FT‐VSS) pulse trains with the conventional flow‐dephasing VSS techniques for CBV quantification.MethodsThe proposed FT‐VSS label and control modules were compared with VSS pulse trains utilizing double refocused hyperbolic tangent (DRHT) and 8‐segment B1‐insensitive rotation (BIR‐8). This was done using both numerical simulations and phantom studies to evaluate their sensitivities to gradient imperfections such as eddy currents. DRHT, BIR‐8, and FT‐VSS prepared CBV mapping was further compared for velocity‐encoding gradients along 3 orthogonal directions in healthy subjects at 3T.ResultsThe phantom studies exhibited more consistent immunity to gradient imperfections for the utilized FT‐VS...

Research paper thumbnail of Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research

Pediatric Neurology, 2016

Research paper thumbnail of Hemorrhage Rates From Brain Arteriovenous Malformation in Patients With Hereditary Hemorrhagic Telangiectasia

Stroke; a journal of cerebral circulation, Jan 9, 2015

Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous ... more Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs). We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis. The majority of patients were women (58%) and white (98%). The mean age at BAVM diagnosis was 31±19 years (range, 0-70), with 61% of cases diagnosed on asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42-2.44%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher ...

Research paper thumbnail of Proton MR Spectroscopy in the Diagnostic Evaluation of Suspected Mitochondrial Disease in Iran

Iranian journal of child neurology, 2013

Mitochondrial diseases are a group of inherited disorders Caused by a derangement of mitochondria... more Mitochondrial diseases are a group of inherited disorders Caused by a derangement of mitochondrial respiration. The clinical manifestations are heterogeneous, and the diagnosis is often based on information acquired from multiple levels of inquiry that require a variety of diagnostic tests for proper determination. Neuroimaging may play a significant role in diagnosis. The various modalities of nuclear magnetic resonance imaging (MRI) allow for multiple independent detection procedures that can give important anatomical and metabolic clues for diagnosis when the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. The non-invasive nature of neuroimaging also allows for longitudinal studies. To date, no pathognomonic correlation between specific genetic defect and neuroimaging findings have been described. The de...

Research paper thumbnail of ATIM-06. A pilot Study of Stereotactic Radiosurgery (SRS) Combined with Ipilimumab Prolonged Survival in Patients with Newly Diagnosed Melanoma Brain Metastases

Neuro-Oncology, 2017

NEURO-ONCOLOGY • NOVEMBER 2017 include overall survival, development of brain metastases, neuroco... more NEURO-ONCOLOGY • NOVEMBER 2017 include overall survival, development of brain metastases, neurocognitive function, and QOL outcomes. TRIAL DESIGN: This is a prospective, singlearm, open-label multicenter pilot study. All patients will undergo TTFields treatment using the NovoTTF-200A System set to an output frequency of 200 kHz. The feasibility of TTFields prophylaxis will be measured as the percentage of patients continuing TTFields therapy until intracranial tumor progression, discontinuation due to disease limiting toxicity, or continuation of therapy for at least 6 months. TTFields will be discontinued in patients who develop intracranial failure while on therapy. All patients who develop intracranial failure may undergo whole brain radiotherapy or best supportive care at the discretion of the treating physician. All study follow-up procedures are to continue according to protocol until death, or until another criteria for removal is met. Because the primary endpoint is feasibility, the proposed sample size is not driven by statistical hypotheses. A sample size of 25 was set to accumulate more extensive patient data for planning the next clinical phase of this potential prophylactic treatment.

Research paper thumbnail of NIMG-97. Echo-Planar MR Spectroscopic Imaging in High Grade Glioma: Effect of Radiotherapy Treatment (RT)

Neuro-Oncology, 2017

Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyo... more Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyond the solid tumor mass, invariably affecting the non-lesional hemisphere. In contrast, patients suffering from LGGs showed less damage to functional connectivity, which was mostly confined to the lesion-bearing hemisphere. In general, the degree of damage to functional connectivity was likely dominated by tumor histology, e.g. HGGs caused far more extensive damage to functional connectivity than LGGs. CONCLUSION: rsfMRI is a novel, non-invasive and easily implementable diagnostic tool in glioma patients which could discover characteristic disturbances in the non-lesional hemisphere of HGG patients. The correlation with tumor grading suggests that rsfMRI has great potential serve as an imaging biomarker for disease burden in glioma patients.

Research paper thumbnail of Osteogenesis Imperfecta of the Temporal Bone 1

A 36-year-old African-American woman who had a history of fluctuating bilateral mixed hearing los... more A 36-year-old African-American woman who had a history of fluctuating bilateral mixed hearing loss that was worse on the left side than on the right complained of worsening of hearing on the right side during follow-up. At physical examination, she was a short obese woman who was wheelchair bound. The scleras were discolored. The tympanic membranes were intact. Audiogram findings demonstrated profound hearing loss on the left side and moderately severe mixed conductive and sensorineural hearing loss on the right side. In the past, she had fluctuations in her hearing with overall progressive deterioration; steroid treatment was unsuccessful. Unenhanced computed tomographic (CT) scans of the petrous temporal bones were obtained with a bone algorithm. Transverse scans of the right side (Fig 1a, 1b) and coronal scans (Fig 1c, 1d) of both sides were obtained.

Research paper thumbnail of Genotype–Phenotype Correlations in Children with HHT

Journal of Clinical Medicine, 2020

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by m... more Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG, ACVRL1, and SMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype–phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype–phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0–18 years; mean: 11 years), ENG mutation was associated with the presence of pulmonary AVMs (p < 0.001) and brain VM (p < 0.001). The presenc...

Research paper thumbnail of NIMG-55. A Quantitative Analysis of Brain Volume Dynamics in PCNSL Patients Treated with High-Dose Methotrexate-Based Therapy

Neuro-Oncology, 2020

BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (... more BACKGROUND Primary CNS lymphoma (PCNSL) is a rare, infiltrative disease. High-dose methotrexate (HD-MTX) is the backbone of induction regimens for PCNSL. While MTX-associated white matter changes are well-described, treatment-related brain volume loss is much less understood, especially in radiotherapy-naïve cohorts. Here, we aimed to longitudinally quantify the rates of brain volume loss in PCNSL patients treated with HD-MTX. SUBJECTS/METHODS We included 12 radiotherapy-naïve patients (age mean±SD 61±15y, range 37-84y, 9F) with histopathologically confirmed PCNSL who received HD-MTX induction (mean±SD 12±4 cycles, range 8-18) +/-rituximab. MRIs were collected from within 1 month of HD-MTX initiation until the end of follow-up (mean±SD: 3.7±2.9y). Longitudinal whole-brain segmentation was performed on FLAIR images using the Sequence Adaptive Multimodal Segmentation tool of FreeSurfer. Brain volumes were normalized to the initial scan, white matter lesion volumes were normalized to c...