Assistant Professor - University Medical Line, Radiology
Honors & Awards
Thrall Innovation Grant, Department of Radiology, Massachusetts General Hospital (2021)
ASNR20 Head and Neck Outstanding Presentation Award, American Society of Neuroradiology (2020)
Alpha Omega Alpha, Stanford (2018)
Moskowitz Research Award, The Moskowitz Fund; Stanford Radiology (2015)
Gates Cambridge Scholarship, Bill and Melinda Gates Foundation (2007)
Overseas Research Scholars Award, Secretary of State for Education and Science, United Kingdom (2007)
William Welch Award, Johns Hopkins School of Medicine (2007)
Phi Beta Kappa (junior class induction), Johns Hopkins University (2003)
Provost's Undergraduate Research Award, Johns Hopkins University (2002)
Woodrow Wilson Undergraduate Research Fellowship, Johns Hopkins University (2002)
Fellowship, Massachusetts General Hospital, Neuroradiology (Chief Fellow 2019-2020) (2020)
Residency, Stanford Heath Care, Diagnostic Radiology (Chief Resident 2017-2018) (2018)
MD, Johns Hopkins School of Medicine, Medicine (2012)
PhD, Cambridge University (Trinity College), Physiology, development and neuroscience (2010)
BA, Johns Hopkins University, Neuroscience (2005)
Current Research and Scholarly Interests
Intracranial Densitometry-Augmented Machine Learning Enhances the Prognostic Value of Brain CT in Pediatric Patients With Traumatic Brain Injury: A Retrospective Pilot Study.
Frontiers in pediatrics
2021; 9: 750272
Background: The inter- and intrarater variability of conventional computed tomography (CT) classification systems for evaluating the extent of ischemic-edematous insult following traumatic brain injury (TBI) may hinder the robustness of TBI prognostic models. Objective: This study aimed to employ fully automated quantitative densitometric CT parameters and a cutting-edge machine learning algorithm to construct a robust prognostic model for pediatric TBI. Methods: Fifty-eight pediatric patients with TBI who underwent brain CT were retrospectively analyzed. Intracranial densitometric information was derived from the supratentorial region as a distribution representing the proportion of Hounsfield units. Furthermore, a machine learning-based prognostic model based on gradient boosting (i.e., CatBoost) was constructed with leave-one-out cross-validation. At discharge, the outcome was assessed dichotomously with the Glasgow Outcome Scale (favorability: 1-3 vs. 4-5). In-hospital mortality, length of stay (>1 week), and need for surgery were further evaluated as alternative TBI outcome measures. Results: Densitometric parameters indicating reduced brain density due to subtle global ischemic changes were significantly different among the TBI outcome groups, except for need for surgery. The skewed intracranial densitometry of the unfavorable outcome became more distinguishable in the follow-up CT within 48 h. The prognostic model augmented by intracranial densitometric information achieved adequate AUCs for various outcome measures [favorability = 0.83 (95% CI: 0.72-0.94), in-hospital mortality = 0.91 (95% CI: 0.82-1.00), length of stay = 0.83 (95% CI: 0.72-0.94), and need for surgery = 0.71 (95% CI: 0.56-0.86)], and this model showed enhanced performance compared to the conventional CRASH-CT model. Conclusion: Densitometric parameters indicative of global ischemic changes during the acute phase of TBI are predictive of a worse outcome in pediatric patients. The robustness and predictive capacity of conventional TBI prognostic models might be significantly enhanced by incorporating densitometric parameters and machine learning techniques.
View details for DOI 10.3389/fped.2021.750272
View details for PubMedID 34796154
View details for PubMedCentralID PMC8593245
The utility of intra-oral ultrasound in improving deep margin clearance of oral tongue cancer resections.
2021; 122: 105512
To investigate the potential utility of intra-oral ultrasound (IOUS) in guiding deep margin clearance and measuring depth of invasion (DOI) of oral tongue carcinomas (OTC).Retrospective chart review of consecutive patients with T1-T3 OTC who underwent intraoperative ultrasound-guided resection and a comparator group that had undergone resection without the use of IOUS both by a single surgeon. Data was extracted from operative, pathology and radiology reports. Deep margins and DOI were reviewed by a dedicated head and neck pathologist. Correlation between histologic and ultrasound DOI was assessed using Pearson correlation.A total of 23 patients were included in the study cohort with a comparator group of 21 patients in the control group. None of the patients in the study cohort had a positive (cut-through) deep margin and the mean deep margin clearance was 8.5 ± 4.9 and 6.7 ± 3.8 for the IOUS and non-IOUS groups respectively (p-value 0.18) showing a non-significant improvement in the IOUS group. As a secondary outcome, there was a strong correlation between histologic and ultrasound DOI (0.9449).Ultrasound appears to be a potentially effective tool in guiding OTC resections. In this small series, IOUS facilitated deep margin clearance and resulted in a non-statistically significant increase in deep margin clearance. Intraoral ultrasound can accurately measure lesional DOI.
View details for DOI 10.1016/j.oraloncology.2021.105512
View details for PubMedID 34564016
- Case 30-2021: A 47-Year-Old Man with Recurrent Unilateral Head and Neck Pain NEW ENGLAND JOURNAL OF MEDICINE 2021; 385 (14): 1317-1325
Severity of Chest Imaging is Correlated with Risk of Acute Neuroimaging Findings among Patients with COVID-19.
AJNR. American journal of neuroradiology
2021; 42 (5): 831-837
Severe respiratory distress in patients with COVID-19 has been associated with higher rate of neurologic manifestations. Our aim was to investigate whether the severity of chest imaging findings among patients with coronavirus disease 2019 (COVID-19) correlates with the risk of acute neuroimaging findings.This retrospective study included all patients with COVID-19 who received care at our hospital between March 3, 2020, and May 6, 2020, and underwent chest imaging within 10 days of neuroimaging. Chest radiographs were assessed using a previously validated automated neural network algorithm for COVID-19 (Pulmonary X-ray Severity score). Chest CTs were graded using a Chest CT Severity scoring system based on involvement of each lobe. Associations between chest imaging severity scores and acute neuroimaging findings were assessed using multivariable logistic regression.Twenty-four of 93 patients (26%) included in the study had positive acute neuroimaging findings, including intracranial hemorrhage (n = 7), infarction (n = 7), leukoencephalopathy (n = 6), or a combination of findings (n = 4). The average length of hospitalization, prevalence of intensive care unit admission, and proportion of patients requiring intubation were significantly greater in patients with acute neuroimaging findings than in patients without them (P < .05 for all). Compared with patients without acute neuroimaging findings, patients with acute neuroimaging findings had significantly higher mean Pulmonary X-ray Severity scores (5.0 [SD, 2.9] versus 9.2 [SD, 3.4], P < .001) and mean Chest CT Severity scores (9.0 [SD, 5.1] versus 12.1 [SD, 5.0], P = .041). The pulmonary x-ray severity score was a significant predictor of acute neuroimaging findings in patients with COVID-19.Patients with COVID-19 and acute neuroimaging findings had more severe findings on chest imaging on both radiographs and CT compared with patients with COVID-19 without acute neuroimaging findings. The severity of findings on chest radiography was a strong predictor of acute neuroimaging findings in patients with COVID-19.
View details for DOI 10.3174/ajnr.A7032
View details for PubMedID 33541897
View details for PubMedCentralID PMC8115353
- Brachiocephalic vein compression with jugular venous reflux may mimic cavernous dural arteriovenous fistula on arterial spin labeling NEURORADIOLOGY 2021; 63 (3): 291-294
Blood Flow Imaging in the Neonatal Brain Using Angular Coherence Power Doppler
IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
2021; 68 (1): 92–106
Using ultrasound to image small vessels in the neonatal brain can be difficult in the presence of strong clutter from the surrounding tissue and with a neonate motion during the scan. We propose a coherence-based beamforming method, namely the short-lag angular coherence (SLAC) beamforming that suppresses incoherent noise and motion artifacts in Ultrafast data, and we demonstrate its applicability to improve detection of blood flow in the neonatal brain. Instead of estimating spatial coherence across the receive elements, SLAC utilizes the principle of acoustic reciprocity to estimate angular coherence from the beamsummed signals from different plane-wave transmits, which makes it computationally efficient and amenable to advanced beamforming techniques, such as f-k migration. The SLAC images of a simulated speckle phantom show similar edge resolution and texture size as the matching B-mode images, and reduced random noise in the background. We apply SLAC power Doppler (PD) to free-hand imaging of neonatal brain vasculature with long Doppler ensembles and show that: 1) it improves visualization of small vessels in the cortex compared to conventional PD and 2) it can be used for tracking of blood flow in the brain over time, meaning it could potentially improve the quality of free-hand functional ultrasound.
View details for DOI 10.1109/TUFFC.2020.3010341
View details for Web of Science ID 000602706700010
View details for PubMedID 32746214
Comparison between computed tomography and ultrasound for presurgical evaluation of oral tongue squamous cell carcinoma tumor thickness.
American journal of otolaryngology
2021; 42 (6): 103089
To compare the accuracy of oral tongue squamous cell carcinoma (OTSCC) tumor thickness (TT) measured on CT to intraoperative ultrasound (US) and histopathology.Twenty-six patients with OTSCC who underwent tumor resection by a single surgeon with simultaneous intraoperative US between 3/2016 and 4/2019 were prospectively identified, and their data reviewed. TT was independently measured in 19 patients who underwent preoperative CT (cTT) by two neuroradiologists blinded to US and histological results. The confidence level of interpretation of cTT was recorded by each reader using a 5-point Likert scale. The degree of dental artifact on CT was also scored. cTT was compared to TT measured on intraoperative US (uTT) and histopathologic assessment of TT (hTT).OTSCC was visualized on CT in 52% (10/19) and 63% (12/19) of cases for readers 1 and 2, respectively. Mean Likert score was 0.42 for reader 1 and 0.73 for reader 2. Mean cTT of OTSCCs was 5.8 mm +/- 1.7 mm (n = 11). In comparison, mean uTT and hTT were 7.6 mm±3.5 mm and 7.1 +/- 4.2 mm, respectively. The Pearson coefficient (95% confidence interval) was 0.10 (-0.53-0.66) between cTT and hTT (n = 11) and 0.93 (0.74-0.98) between uTT and hTT.Preoperative CT is not reliable for assessment of TT in OTSCC compared to US and histopathology, particularly for OTSCC under 10 mm. US offers a practical complementary imaging tool with a unique role for primary tumor assessment that can aid in pre-operative planning, especially for small tumors.
View details for DOI 10.1016/j.amjoto.2021.103089
View details for PubMedID 34087615
Lung apical findings in coronavirus disease (COVID-19) infection on neck and cervical spine CT.
2020; 27 (6): 731-735
To evaluate the prevalence and features of lung apical findings on neck and cervical spine CTs performed in patients with COVID-19.This was a retrospective, IRB-approved study performed at a large academic hospital in the USA. Between March 3, 2020, and May 6, 2020, 641 patients with COVID-19 infection diagnosed by RT-PCR received medical care at our institution. A small cohort of patients with COVID-19 infection underwent neck or cervical spine CT imaging for indications including stroke, trauma, and neck pain. The lung apices included in the field of view on these CT scans were reviewed for the presence of findings suspicious for COVID-19 pneumonia, including ground-glass opacities, consolidation, or crazy-paving pattern. The type and frequency of these findings were recorded and correlated with clinical information including age, gender, and symptoms.Thirty-four patients had neck or spine CTs performed before or concurrently with a chest CT. Of this group, 17 (50%) had unknown COVID-19 status at the time of neck or spine imaging and 10 (59%) of their CT studies had findings in the lung apices consistent with COVID-19 pneumonia.Lung apical findings on cervical spine or neck CTs consistent with COVID-19 infection are common and may be encountered on neuroimaging performed for non-respiratory indications. For these patients, the emergency radiologist may be the first physician to suspect underlying COVID-19 infection.
View details for DOI 10.1007/s10140-020-01822-0
View details for PubMedID 32696116
View details for PubMedCentralID PMC7372543
- Risk of Acute Cerebrovascular Events in Patients with COVID-19 Infection. AJNR. American journal of neuroradiology 2020; 41 (11): E92-E93
- Chest CT Scanning in Suspected Stroke: Not Always Worth the Extra Mile. AJNR. American journal of neuroradiology 2020; 41 (11): E86-E87
Paraspinal Myositis in Patients with COVID-19 Infection.
AJNR. American journal of neuroradiology
2020; 41 (10): 1949-1952
Myalgia is a previously reported symptom in patients with COVID-19 infection; however, the presence of paraspinal myositis has not been previously reported. We report MR imaging findings of the spine obtained in a cohort of 9 patients with COVID-19 infection who presented to our hospital between March 3, 2020 and May 6, 2020. We found that 7 of 9 COVID-19 patients (78%) who underwent MR imaging of the spine had MR imaging evidence of paraspinal myositis, characterized by intramuscular edema and/or enhancement. Five of these 7 patients had a prolonged hospital course (greater than 25 days). Our knowledge of the imaging manifestations of COVID-19 infection is expanding. It is important for clinicians>a to be aware of the relatively high frequency of paraspinal myositis in this small cohort of patients with COVID-19 infection.
View details for DOI 10.3174/ajnr.A6711
View details for PubMedID 32763902
View details for PubMedCentralID PMC7661075
Clinical and Neuroimaging Correlation in Patients with COVID-19.
AJNR. American journal of neuroradiology
2020; 41 (10): 1791-1796
Coronavirus disease 2019 (COVID-19) is increasingly being recognized for its multiorgan involvement, including various neurological manifestations. We examined the frequency of acute intracranial abnormalities seen on CT and/or MR imaging in patients with COVID-19 and investigated possible associations between these findings and clinical parameters, including length of hospital stay, requirement for intubation, and development of acute kidney injury.This was a retrospective study performed at a large academic hospital in the United States. A total of 641 patients presented to our institution between March 3, 2020, and May 6, 2020, for treatment of coronavirus disease 2019, of whom, 150 underwent CT and/or MR imaging of the brain. CT and/or MR imaging examinations were evaluated for the presence of hemorrhage, infarction, and leukoencephalopathy. The frequency of these findings was correlated with clinical variables, including body mass index, length of hospital stay, requirement for intubation, and development of acute kidney injury as documented in the electronic medical record.Of the 150 patients, 26 (17%) had abnormal CT and/or MR imaging findings, with hemorrhage in 11 of the patients (42%), infarction in 13 of the patients (50%), and leukoencephalopathy in 7 of the patients (27%). Significant associations were seen between abnormal CT/MR imaging findings and intensive care unit admission (P = .039), intubation (P = .004), and acute kidney injury (P = .030).A spectrum of acute neuroimaging abnormalities was seen in our cohort of patients with coronavirus disease 2019, including hemorrhage, infarction, and leukoencephalopathy. Significant associations between abnormal neuroimaging studies and markers of disease severity (intensive care unit admission, intubation, and acute kidney injury) suggest that patients with severe forms of coronavirus disease 2019 may have higher rates of neuroimaging abnormalities.
View details for DOI 10.3174/ajnr.A6717
View details for PubMedID 32912875
View details for PubMedCentralID PMC7661080
Comparison of Intraoperative Sonography and Histopathologic Evaluation of Tumor Thickness and Depth of Invasion in Oral Tongue Cancer: A Pilot Study.
AJNR. American journal of neuroradiology
2020; 41 (7): 1245-1250
For primary squamous cell carcinoma of the oral tongue, accurate assessment of tumor thickness and depth of invasion is critical for staging and operative management. Currently, typical imaging modalities used for preoperative staging are CT and MR imaging. Intraoperatively, CT or MR imaging cannot provide real-time guidance, and assessment by manual palpation is limited in precision. We investigated whether intraoperative sonography is a feasible technique for assessment of tumor thickness and depth of invasion and validated its accuracy by comparing it with histopathologic evaluation of the resected specimen.Twenty-six patients with squamous cell carcinoma of the oral tongue who underwent tumor resection by a single surgeon between March 31, 2016, and April 26, 2019, were prospectively identified. Intraoperative sonography was obtained in planes longitudinal and transverse to the long axis of the tumor. Twenty-two patients had archived images that allowed measurements of tumor thickness and depth of invasion sonographically. Two patients had dysplasia and were excluded. The remaining 20 patients had histologic tumor thickness and histologic depth of invasion measured by a single pathologist.The mean sonographic tumor thickness was 7.5 ± 3.5 mm, and the mean histologic tumor thickness was 7.0 ± 4.2 mm. Mean sonographic depth of invasion and histologic depth of invasion were 6.6 ± 3.4 and 6.4 ± 4.4 mm, respectively. There was excellent correlation between sonographic and histologic measurements for both tumor thickness and depth of invasion with Pearson correlation coefficients of 0.95 (95% CI, 0.87-0.98) and 0.95 (95% CI, 0.87-0.98), respectively.Intraoperative sonography can provide reliable, real-time assessment of the extent of tongue tumors.
View details for DOI 10.3174/ajnr.A6625
View details for PubMedID 32554422
View details for PubMedCentralID PMC7357662
Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters.
2019; 206: 73–86
Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body.
View details for PubMedID 30953907
Evaluation of Thick-Slab Overlapping MIP Images of Contrast-Enhanced 3D T1-Weighted CUBE for Detection of Intracranial Metastases: A Pilot Study for Comparison of Lesion Detection, Interpretation Time, and Sensitivity with Nonoverlapping CUBE MIP, CUBE, and Inversion-Recovery-Prepared Fast-Spoiled Gradient Recalled Brain Volume.
AJNR. American journal of neuroradiology
Early and accurate identification of cerebral metastases is important for prognostication and treatment planning although this process is often time consuming and labor intensive, especially with the hundreds of images associated with 3D volumetric imaging. This study aimed to evaluate the benefits of thick-slab overlapping MIPs constructed from contrast-enhanced T1-weighted CUBE (overlapping CUBE MIP) for the detection of brain metastases in comparison with traditional CUBE and inversion-recovery prepared fast-spoiled gradient recalled brain volume (IR-FSPGR-BRAVO) and nonoverlapping CUBE MIP.A retrospective review of 48 patients with cerebral metastases was performed at our institution from June 2016 to October 2017. Brain MRIs, which were acquired on multiple 3T scanners, included gadolinium-enhanced T1-weighted IR-FSPGR-BRAVO and CUBE, with subsequent generation of nonoverlapping CUBE MIP and overlapping CUBE MIP. Two blinded radiologists identified the total number and location of metastases on each image type. The Cohen κ was used to determine interrater agreement. Sensitivity, interpretation time, and lesion contrast-to-noise ratio were assessed.Interrater agreement for identification of metastases was fair-to-moderate for all image types (κ = 0.222-0.598). The total number of metastases identified was not significantly different across the image types. Interpretation time for CUBE MIPs was significantly shorter than for CUBE and IR-FSPGR-BRAVO, saving at least 50 seconds per case on average (P < .001). The mean lesion contrast-to-noise ratio for both CUBE MIPs was higher than for IR-FSPGR-BRAVO. The mean contrast-to-noise ratio for small lesions (<4 mm) was lower for nonoverlapping CUBE MIP (1.55) than for overlapping CUBE MIP (2.35). For both readers, the sensitivity for lesion detection was high for all image types but highest for overlapping CUBE MIP and CUBE (0.93-0.97).This study suggests that the use of overlapping CUBE MIP or nonoverlapping CUBE MIP for the detection of brain metastases can reduce interpretation time without sacrificing sensitivity, though the contrast-to-noise ratio of lesions is highest for overlapping CUBE MIP.
View details for DOI 10.3174/ajnr.A5747
View details for PubMedID 30093483
Current Clinical State of Advanced Magnetic Resonance Imaging for Brain Tumor Diagnosis and Follow Up.
Seminars in roentgenology
2018; 53 (1): 45–61
View details for PubMedID 29405955
Changes in the gray and white matter of patients with ischemic-edematous insults after traumatic brain injury.
Journal of neurosurgery
OBJECTIVE: Gray matter (GM) and white matter (WM) are vulnerable to ischemic-edematous insults after traumatic brain injury (TBI). The extent of secondary insult after brain injury is quantifiable using quantitative CT analysis. One conventional quantitative CT measure, the gray-white matter ratio (GWR), and a more recently proposed densitometric analysis are used to assess the extent of these insults. However, the prognostic capacity of the GWR in patients with TBI has not yet been validated. This study aims to test the prognostic value of the GWR and evaluate the alternative parameters derived from the densitometric analysis acquired during the acute phase of TBI. In addition, the prognostic ability of the conventional TBI prognostic models (i.e., IMPACT [International Mission for Prognosis and Analysis of Clinical Trials in TBI] and CRASH [Corticosteroid Randomisation After Significant Head Injury] models) were compared to that of the quantitative CT measures. METHODS: Three hundred patients with TBI of varying ages (92 pediatric, 94 adult, and 114 geriatric patients) and admitted between 2008 and 2013 were included in this retrospective cohort study. The normality of the density of the deep GM and whole WM was evaluated as the proportion of CT pixels with Hounsfield unit values of 31-35 for GM and 26-30 for WM on CT images of the entire supratentorial brain. The outcome was evaluated using the Glasgow Outcome Scale (GOS) at discharge (GOS score ≤ 3, n = 100). RESULTS: Lower proportions of normal densities in the deep GM and whole WM indicated worse outcomes. The proportion of normal WM exhibited a significant prognostic capacity (area under the curve [AUC] = 0.844). The association between the outcome and the normality of the WM density was significant in adult (AUC = 0.792), pediatric (AUC = 0.814), and geriatric (AUC = 0.885) patients. In pediatric patients, the normality of the overall density and the density of the GM were indicative of the outcome (AUC = 0.751). The average GWR was not associated with the outcome (AUC = 0.511). IMPACT and CRASH models showed adequate and reliable performance in the pediatric and geriatric groups but not in the adult group. The highest overall predictive performance was achieved by the densitometry-augmented IMPACT model (AUC = 0.881). CONCLUSIONS: Both deep GM and WM are susceptible to ischemic-edematous insults during the early phase of TBI. The extent of the secondary injury was better evaluated by analyzing the normality of the deep GM and WM rather than by calculating the GWR.
View details for PubMedID 30485242
CORRELATION OF VASARI-BASED MRI PHENOTYPES WITH MGMT AND IDH STATUS ACROSS GLIOMA GRADES: A STATISTICAL ANALYSIS IN 372 PATIENTS
OXFORD UNIV PRESS INC. 2017: 150
View details for Web of Science ID 000415152502222
THE EFFECT OF PATIENT AGE AT GLIOMA PRESENTATION ON MRI PHENOTYPE: A COMPREHENSIVE ANALYSIS OF VASARI-BASED FEATURE-SET CRITERIA IN 711 PATIENTS
OXFORD UNIV PRESS INC. 2017: 158
View details for Web of Science ID 000415152503005
Abilities of a Densitometric Analysis of Computed Tomography Images and Hemorrhagic Parameters to Predict Outcome Favorability in Patients With Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. A rapid assessment of ICH severity involves the use of computed tomography (CT) and derivation of the hemorrhage volume, which is often estimated using the ABC/2 method. However, these estimates are highly inaccurate and may not be feasible for anticipating outcome favorability.To predict patient outcomes via a quantitative, densitometric analysis of CT images, and to compare the predictive power of these densitometric parameters with the conventional ABC/2 volumetric parameter and segmented hemorrhage volumes.Noncontrast CT images of 87 adult patients with ICH (favorable outcomes = 69, unfavorable outcomes = 12, and deceased = 6) were analyzed. In-house software was used to calculate the segmented hemorrhage volumes, ABC/2 and densitometric parameters, including the skewness and kurtosis of the density distribution, interquartile ranges, and proportions of specific pixels in sets of CT images. Nonparametric statistical analyses were conducted.The densitometric parameter interquartile range exhibited greatest accuracy (82.7%) in predicting favorable outcomes. The combination of skewness and the interquartile range effectively predicted mortality (accuracy = 83.3%). The actual volume of the ICH exhibited good coherence with ABC/2 (R = 0.79). Both parameters predicted mortality with moderate accuracy (<78%) but were less effective in predicting unfavorable outcomes.Hemorrhage volume was rapidly estimated and effectively predicted mortality in patients with ICH; however, this value may not be useful for predicting favorable outcomes. The densitometric analysis exhibited significantly higher power in predicting mortality and favorable outcomes in patients with ICH.
View details for DOI 10.1093/neuros/nyx379
View details for PubMedID 28973583
Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption?
JOURNAL OF NEUROSURGERY
2016; 124 (2): 334-341
Periventricular lucency (PVL) is often observed in the hydrocephalic brain on CT or MRI. Earlier studies have proposed the extravasation of ventricular CSF into the periventricular white matter or transependymal CSF absorption as possible causes of PVL in hydrocephalus. However, there is insufficient evidence for either theory to be conclusive.A finite element (FE) model of the hydrocephalic brain with detailed anatomical geometry was constructed to investigate the possible mechanism of PVL in hydrocephalus. The initiation of hydrocephalus was modeled by applying a transmantle pressure gradient (TPG). The model was exposed to varying TPGs to investigate the effects of different geometrical characteristics on the distribution of PVL. The edema map was derived based on the interstitial pore pressure.The model simulated the main radiological features of hydrocephalus, i.e., ventriculomegaly and PVL. The degree of PVL, assessed by the pore pressure, was prominent in mild to moderate ventriculomegaly. As the degree of ventriculomegaly exceeded certain values, the pore pressure across the cerebrum became positive, thus inducing the disappearance of PVL.The results are in accordance with common clinical findings of PVL. The degree of ventriculomegaly significantly influences the development of PVL, but two factors were not linearly correlated. The results are indicative of the transependymal CSF absorption as a possible cause of PVL, but the extravasation theory cannot be formally rejected.
View details for DOI 10.3171/2014.11.JNS141382
View details for PubMedID 26274984
Finite element analysis for normal pressure hydrocephalus: The effects of the integration of sulci
MEDICAL IMAGE ANALYSIS
2015; 24 (1): 235-244
Finite element analysis (FEA) is increasingly used to investigate the brain under various pathological changes. Although FEA has been used to study hydrocephalus for decades, previous studies have primarily focused on ventriculomegaly. The present study aimed to investigate the pathologic changes regarding sulcal deformation in normal pressure hydrocephalus (NPH). Two finite element (FE) models-an anatomical brain geometric (ABG) model and the conventional simplified brain geometric (SBG) model-of NPH were constructed. The models were constructed with identical boundary conditions but with different geometries. The ABG model contained details of the sulci geometry, whereas these details were omitted from the SBG model. The resulting pathologic changes were assessed via four biomechanical parameters: pore pressure, von Mises stress, pressure, and void ratio. NPH was induced by increasing the transmantle pressure gradient (TPG) from 0 to a maximum of 2.0 mmHg. Both models successfully simulated the major features of NPH (i.e., ventriculomegaly and periventricular lucency). The changes in the biomechanical parameters with increasing TPG were similar between the models. However, the SBG model underestimated the degree of stress across the cerebral mantle by 150% compared with the ABG model. The SBG model also overestimates the degree of ventriculomegaly (increases of 194.5% and 154.1% at TPG = 2.0 mmHg for the SBG and ABG models, respectively). Including the sulci geometry in a FEA for NPH clearly affects the overall results. The conventional SBG model is inferior to the ABG model, which accurately simulated sulcal deformation and the consequent effects on cortical or subcortical structures. The inclusion of sulci in future FEA for the brain is strongly advised, especially for models used to investigate space-occupying lesions.
View details for DOI 10.1016/j.media.2015.05.006
View details for PubMedID 26208335
Thresholds of resistance to CSF outflow in predicting shunt responsiveness
2015; 37 (4): 332-340
Disturbances in cerebrospinal fluid (CSF) absorption capacity represent one of the primary causes of normal pressure hydrocephalus (NPH). The resistance to CSF outflow (Rout) may reflect the severity of this disturbance and has been used as a supplementary parameter to predict shunt responsiveness. However, there is no widely accepted threshold of Rout in this scenario. This study aimed to determine the most appropriate threshold through meta-analyses.A total of four previously reported cutoff values of Rout (10, 12, 15, and 18 mmHg/ml/minutes) were selected as potential thresholds. A systematic review of existing studies involving NPH, shunt surgeries, and Rout was conducted. The pooled results from retrieved articles were subjected to statistical analyses.A total of nine studies were included in the meta-analyses based on the available preoperative Rout and postoperative improvement of subjects. The odds ratios of the four thresholds were 2·82, 3·58, 2·72, and 2·38 for 10, 12, 15, and 18 mmHg/ml/minutes of Rout, respectively. The Rout of 12 mmHg/ml/minutes yielded high accuracy (72·95%), high sensitivity (80·26%), and moderate specificity (46·79%).The presented study conducted meta-analyses and revealed that a Rout of 12 mmHg/ml/minutes is the most suitable threshold for predicting shunt responsiveness in NPH patients.
View details for DOI 10.1179/1743132814Y.0000000454
View details for Web of Science ID 000347918400008
View details for PubMedID 25323618
National trends in burn and inhalation injury in burn patients: results of analysis of the nationwide inpatient sample database.
Journal of burn care & research
2015; 36 (2): 258-265
The aim of this study was describe national trends in prevalence, demographics, hospital length of stay (LOS), hospital charges, and mortality for burn patients with and without inhalational injury and to compare to the National Burn Repository. Burns and inhalation injury cause considerable mortality and morbidity in the United States. There remains insufficient reporting of the demographics and outcomes surrounding such injuries. The National Inpatient Sample database, the nation's largest all-payer inpatient care data repository, was utilized to select 506,628 admissions for burns from 1988 to 2008 based on ICD-9-CM recording. The data were stratified based on the extent of injury (%TBSA) and presence or absence of inhalational injury. Inhalation injury was observed in only 2.2% of burns with <20% TBSA but 14% of burns with 80 to 99% TBSA. Burn patients with inhalation injury were more likely to expire in-hospital compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P < .001). Other factors associated with higher mortality were African-American race, female sex, and urban practice setting. Patients treated at rural facilities and patients with hyperglycemia had lower mortality rates. Each increase in percent of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The median in-hospital charge for a burn patient with inhalation injury was US$32,070, compared to US$17,600 for those without. Overall, patients who expired from burn injury accrued higher in-hospital charges (median, US$50,690 vs US$17,510). Geographically, California and New Jersey were the states with the highest charges, whereas Vermont and Maryland were states with the lowest charges. The study analysis provides a broad sampling of nationwide demographics, LOS, and in-hospital charges for patients with burns and inhalation injury.
View details for DOI 10.1097/BCR.0000000000000064
View details for PubMedID 24918946
Quantitative analysis of computed tomography images and early detection of cerebral edema for pediatric traumatic brain injury patients: retrospective study
The purpose of this study was to identify whether the distribution of Hounsfield Unit (HU) values across the intracranial area in computed tomography (CT) images can be used as an effective diagnostic tool for determining the severity of cerebral edema in pediatric traumatic brain injury (TBI) patients.CT images, medical records and radiology reports on 70 pediatric patients were collected. Based on radiology reports and the Marshall classification, the patients were grouped as mild edema patients (n=37) or severe edema patients (n=33). Automated quantitative analysis using unenhanced CT images was applied to eliminate artifacts and identify the difference in HU value distribution across the intracranial area between these groups.The proportion of pixels with HU=17 to 24 was highly correlated with the existence of severe cerebral edema (P<0.01). This proportion was also able to differentiate patients who developed delayed cerebral edema from mild TBI patients. A significant difference between deceased patients and surviving patients in terms of the HU distribution came from the proportion of pixels with HU=19 to HU=23 (P<0.01).The proportion of pixels with an HU value of 17 to 24 in the entire cerebral area of a non-enhanced CT image can be an effective basis for evaluating the severity of cerebral edema. Based on this result, we propose a novel approach for the early detection of severe cerebral edema.
View details for DOI 10.1186/s12916-014-0186-2
View details for Web of Science ID 000344893100001
View details for PubMedCentralID PMC4219082
Axonal mRNA localization and local protein synthesis in nervous system assembly, maintenance and repair
NATURE REVIEWS NEUROSCIENCE
2012; 13 (5): 308-324
mRNAs can be targeted to specific neuronal subcellular domains, which enables rapid changes in the local proteome through local translation. This mRNA-based mechanism links extrinsic signals to spatially restricted cellular responses and can mediate stimulus-driven adaptive responses such as dendritic plasticity. Local mRNA translation also occurs in growing axons where it can mediate directional responses to guidance signals. Recent profiling studies have revealed that both growing and mature axons possess surprisingly complex and dynamic transcriptomes, thereby suggesting that axonal mRNA localization is highly regulated and has a role in a broad range of processes, a view that is increasingly being supported by new experimental evidence. Here, we review current knowledge on the roles and regulatory mechanisms of axonal mRNA translation and discuss emerging links to axon guidance, survival, regeneration and neurological disorders.
View details for DOI 10.1038/nrn3210
View details for Web of Science ID 000303059600010
View details for PubMedID 22498899
View details for PubMedCentralID PMC3682205
14-3-3 proteins regulate retinal axon growth by modulating ADF/cofilin activity
2012; 72 (4): 600-614
Precise navigation of axons to their targets is critical for establishing proper neuronal networks during development. Axon elongation, whereby axons extend far beyond the site of initiation to reach their target cells, is an essential step in this process, but the precise molecular pathways that regulate axon growth remain uncharacterized. Here we show that 14-3-3/14-3-3ς proteins-adaptor proteins that modulate diverse cellular processes including cytoskeletal dynamics-play a critical role in Xenopus retinal ganglion cell (RGC) axon elongation in vivo and in vitro. We have identified the expression of 14-3-3/14-3-3ς transcripts and proteins in retinal growth cones, with higher levels of expression occurring during the phase of rapid pathway extension. Competitive inhibition of 14-3-3/14-3-3ς by expression of a genetically encoded peptide, R18, in RGCs resulted in a marked decrease in the length of the initial retinotectal projection in vivo and a corresponding decrease in axon elongation rate in vitro (30-40%). Furthermore, 14-3-3/14-3-3ς (R1) co-localized with Xenopus actin depolymerizing factor (ADF)/cofilin (XAC) in RGC growth cones. Inhibition of 14-3-3/14-3-3ς function with either R18 or morpholinos reduced the level of inactive pXAC and increased the sensitivity to collapse by the repulsive cue, Slit2. Collectively, these results demonstrate that14-3-3/14-3-3ς participates in the regulation of retinal axon elongation, in part by modulating XAC activity.
View details for DOI 10.1002/dneu.20955
View details for Web of Science ID 000301282000012
View details for PubMedID 21780304
View details for PubMedCentralID PMC3682208
Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
2012; 148 (4): 752-764
Local protein synthesis plays a key role in regulating stimulus-induced responses in dendrites and axons. Recent genome-wide studies have revealed that thousands of different transcripts reside in these distal neuronal compartments, but identifying those with functionally significant roles presents a challenge. We performed an unbiased screen to look for stimulus-induced, protein synthesis-dependent changes in the proteome of Xenopus retinal ganglion cell (RGC) axons. The intermediate filament protein lamin B2 (LB2), normally associated with the nuclear membrane, was identified as an unexpected major target. Axonal ribosome immunoprecipitation confirmed translation of lb2 mRNA in vivo. Inhibition of lb2 mRNA translation in axons in vivo does not affect guidance but causes axonal degeneration. Axonal LB2 associates with mitochondria, and LB2-deficient axons exhibit mitochondrial dysfunction and defects in axonal transport. Our results thus suggest that axonally synthesized lamin B plays a crucial role in axon maintenance by promoting mitochondrial function.
View details for DOI 10.1016/j.cell.2011.11.064
View details for Web of Science ID 000300622400016
View details for PubMedID 22341447
View details for PubMedCentralID PMC3314965
Local translation and mRNA trafficking in axon pathfinding.
Results and problems in cell differentiation
2009; 48: 269-288
Axons and their growth cones are specialized neuronal sub-compartments that possess translation machinery and have distinct messenger RNAs (mRNAs). Several classes of mRNAs have been identified using candidate-based, as well as unbiased genome-wide-based approaches. Axonal mRNA localization serves to regulate spatially the protein synthesis; thereby, providing axons with a high degree of functional autonomy from the soma during axon pathfinding. Importantly, de novo protein synthesis in navigating axonal growth cones is necessary for chemotropic responses to various axon guidance cues. This chapter discusses the molecular components involved in regulating axonal mRNA trafficking, targeting, and translation, and focuses on RNA binding proteins (RNBPs) and microRNAs. The functional significance of local mRNA translation in the directional response of growth cones to a gradient is highlighted along with the downstream signaling events that mediate local protein synthesis. The view that emerges is that local translation is tightly coupled to extracellular cues, enabling growth cones to respond to new signals with exquisite adaptability and spatiotemporal control.
View details for DOI 10.1007/400_2009_5
View details for PubMedID 19343311
View details for PubMedCentralID PMC3682209