John A. Detre

YNIMG Journal 2026 Journal Article

Age dependence of brain oxygen metabolism in adults assessed by 3D constrained quantitative BOLD MRI

• Kathryn M. Jaroszynski
• Sina Dindarian
• Hyunyeol Lee
• John A. Detre
• Felix W. Wehrli

Global and regional variations in cerebral oxygen metabolism are known to be associated with both healthy aging and the early stages of neurodegeneration. To quantify age effects, a recently developed 3D constrained qBOLD protocol was implemented to determine voxelwise OEF, integrated with ASL-derived CBF measurements to compute CMRO2. Thirty-four healthy adults (23–87 years) were examined to identify global and regional patterns of cerebral oxygen metabolism across younger (<35, n = 15) and older (>50, n = 19) adults. Whole-brain OEF was greater in older than in younger adults (40. 2 ± 5. 1 % vs 34. 5 ± 4. 6 %, P = 0. 002), whereas CBF was lower (39. 5 ± 10. 3 vs 48. 3 ± 8. 3 mL/100g/min, P = 0. 011), resulting in comparable CMRO2 (144. 0 ± 31. 8 vs 150. 7 ± 30. 0 µmol/100g/min, P = 0. 537). Across participants, OEF increased by 1. 5 % and CBF declined by 2. 1 % per decade. Regionally, OEF was greater in older adults within medial temporal lobe (MTL) (37. 4 ± 5. 9 % vs 32. 2 ± 5. 1 %), hippocampus (37. 2 ± 7. 0 % vs 29. 1 ± 6. 1 %), amygdala (38. 3 ± 8. 6 % vs 27. 9 ± 6. 1 %), thalamus (40. 5 ± 6. 4 % vs 32. 5 ± 7. 1 %), striatum (42. 7 ± 5. 3 % vs 36. 2 ± 5. 5 %), frontal (38. 7 ± 5. 2 % vs 34. 7 ± 5. 0 %), parietal (43. 9 ± 5. 1 % vs 38. 2 ± 5. 5 %), and occipital (40. 7 ± 6. 3 % vs 35. 1 ± 5. 3 %) lobes, all P < 0. 05. CMRO2 differed between older vs younger subjects only in the amygdala (126. 6 ± 35. 9 vs 97. 5 ± 31. 6 μmol/min/100 g, P = 0. 01). Exploring regional heterogeneity, MTL and its substructures exhibited reduced OEF relative to whole-brain averages in both groups. Overall findings indicate that cerebral oxygen metabolism remains largely preserved throughout adulthood. The combined qBOLD–ASL technique offers a robust framework for detecting regional variations in brain oxygen metabolism, characterizing both normative cerebrovascular aging and possibly early stages of neurodegeneration.

YNIMG Journal 2022 Journal Article

Cerebellum anatomy predicts individual risk-taking behavior and risk tolerance

• Peng Quan
• Lisheng He
• Tianxin Mao
• Zhuo Fang
• Yao Deng
• Yu Pan
• Xiaocui Zhang
• Ke Zhao

Human risk tolerance is highly idiosyncratic and individuals often show distinctive preferences when faced with similar risky situations. However, the neural underpinnings of individual differences in risk-taking remain unclear. Here we combined structural and perfusion MRI and examined the associations between brain anatomy and individual risk-taking behavior/risk tolerance in a sample of 115 healthy participants during the Balloon Analogue Risk Task, a well-established sequential risky decision paradigm. Both whole brain and region-of-interest analyses showed that the left cerebellum gray matter volume (GMV) has a strong association with individual risk-taking behavior and risk tolerance, outperforming the previously reported associations with the amygdala and right posterior parietal cortex (PPC) GMV. Left cerebellum GMV also accounted for risk tolerance and risk-taking behavior changes with aging. However, regional cerebral blood flow (CBF) provided no additional predictive power. These findings suggest a novel cerebellar anatomical contribution to individual differences in risk tolerance. Further studies are necessary to elucidate the underestimated important role of cerebellum in risk-taking.

YNICL Journal 2022 Journal Article

Ex vivo MRI and histopathology detect novel iron-rich cortical inflammation in frontotemporal lobar degeneration with tau versus TDP-43 pathology

• M. Dylan Tisdall
• Daniel T. Ohm
• Rebecca Lobrovich
• Sandhitsu R. Das
• Gabor Mizsei
• Karthik Prabhakaran
• Ranjit Ittyerah
• Sydney Lim

Frontotemporal lobar degeneration (FTLD) is a heterogeneous spectrum of age-associated neurodegenerative diseases that include two main pathologic categories of tau (FTLD-Tau) and TDP-43 (FTLD-TDP) proteinopathies. These distinct proteinopathies are often clinically indistinguishable during life, posing a major obstacle for diagnosis and emerging therapeutic trials tailored to disease-specific mechanisms. Moreover, MRI-derived measures have had limited success to date discriminating between FTLD-Tau or FTLD-TDP. T2*-weighted (T2*w) ex vivo MRI has previously been shown to be sensitive to non-heme iron in healthy intracortical lamination and myelin, and to pathological iron deposits in amyloid-beta plaques and activated microglia in Alzheimer’s disease neuropathologic change (ADNC). However, an integrated, ex vivo MRI and histopathology approach is understudied in FTLD. We apply joint, whole-hemisphere ex vivo MRI at 7 T and histopathology to the study autopsy-confirmed FTLD-Tau (n = 4) and FTLD-TDP (n = 3), relative to ADNC disease-control brains with antemortem clinical symptoms of frontotemporal dementia (n = 2), and an age-matched healthy control. We detect distinct laminar patterns of novel iron-laden glial pathology in both FTLD-Tau and FTLD-TDP brains. We find iron-positive ameboid and hypertrophic microglia and astrocytes largely in deeper GM and adjacent WM in FTLD-Tau. In contrast, FTLD-TDP presents prominent superficial cortical layer iron reactivity in astrocytic processes enveloping small blood vessels with limited involvement of adjacent WM, as well as more diffuse distribution of punctate iron-rich dystrophic microglial processes across all GM lamina. This integrated MRI/histopathology approach reveals ex vivo MRI features that are consistent with these pathological observations distinguishing FTLD-Tau and FTLD-TDP subtypes, including prominent irregular hypointense signal in deeper cortex in FTLD-Tau whereas FTLD-TDP showed upper cortical layer hypointense bands and diffuse cortical speckling. Moreover, differences in adjacent WM degeneration and iron-rich gliosis on histology between FTLD-Tau and FTLD-TDP were also readily apparent on MRI as hyperintense signal and irregular areas of hypointensity, respectively that were more prominent in FTLD-Tau compared to FTLD-TDP. These unique histopathological and radiographic features were distinct from healthy control and ADNC brains, suggesting that iron-sensitive T2*w MRI, adapted to in vivo application at sufficient resolution, may eventually offer an opportunity to improve antemortem diagnosis of FTLD proteinopathies using tissue-validated methods.

YNIMG Journal 2022 Journal Article

Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans

• Abigail T.J. Cember
• Neil E. Wilson
• Laurie J. Rich
• Puneet Bagga
• Ravi Prakash Reddy Nanga
• Sophia Swago
• Anshuman Swain
• Deepa Thakuri

H MRS acquisition methods, it can be performed using commonly implemented single voxel spectroscopy (SVS) and chemical shift imaging (CSI) sequences. In this work, we implement qMRS in semi-LASER based CSI, generating dynamic maps arising from the fitted spectra, and demonstrating the feasibility of using qMRS and qCSI to monitor dynamic metabolism in the human brain using a 7T scanner with no auxiliary hardware.

YNIMG Journal 2022 Journal Article

Spatially-enhanced clusterwise inference for testing and localizing intermodal correspondence

• Sarah M. Weinstein
• Simon N. Vandekar
• Erica B. Baller
• Danni Tu
• Azeez Adebimpe
• Tinashe M. Tapera
• Ruben C. Gur
• Raquel E. Gur

With the increasing availability of neuroimaging data from multiple modalities-each providing a different lens through which to study brain structure or function-new techniques for comparing, integrating, and interpreting information within and across modalities have emerged. Recent developments include hypothesis tests of associations between neuroimaging modalities, which can be used to determine the statistical significance of intermodal associations either throughout the entire brain or within anatomical subregions or functional networks. While these methods provide a crucial foundation for inference on intermodal relationships, they cannot be used to answer questions about where in the brain these associations are most pronounced. In this paper, we introduce a new method, called CLEAN-R, that can be used both to test intermodal correspondence throughout the brain and also to localize this correspondence. Our method involves first adjusting for the underlying spatial autocorrelation structure within each modality before aggregating information within small clusters to construct a map of enhanced test statistics. Using structural and functional magnetic resonance imaging data from a subsample of children and adolescents from the Philadelphia Neurodevelopmental Cohort, we conduct simulations and data analyses where we illustrate the high statistical power and nominal type I error levels of our method. By constructing an interpretable map of group-level correspondence using spatially-enhanced test statistics, our method offers insights beyond those provided by earlier methods.

YNICL Journal 2020 Journal Article

Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment

• Sudipto Dolui
• Zhengjun Li
• Ilya M. Nasrallah
• John A. Detre
• David A. Wolk

Neurodegenerative biomarkers support diagnosis and measurement of disease progression in the Alzheimer's disease (AD) continuum. 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET), which measures glucose metabolism, is one of the most commonly used biomarkers of neurodegeneration, but is expensive and requires exposure to ionizing radiation. Arterial Spin Labeled (ASL) perfusion Magnetic Resonance Imaging (MRI) provides non invasive quantification of cerebral blood flow (CBF), which is believed to be tightly coupled to glucose metabolism. Here we aimed to compare the performances of ASL derived CBF and 18F-FDG-PET derived standardized uptake value ratio (SUVR) in discriminating patients with mild cognitive impairment (MCI) from older Controls. 2D pseudo continuous ASL and 18F-FDG-PET data with adequate scan quality from 50 MCI study participants (age=73. 0 ± 7. 0 years, 16 female) and 35 older controls (age=70. 2 ± 6. 9 years, 20 female), acquired in close temporal proximity, usually on the same day, were considered for this study. We assessed Control-patient group differences both at voxel level and within a priori regions of interest (ROIs). We also compared their area under receiver operating characteristic curves (AUC) with mean CBF or SUVR in a priori selected posterior cingulate cortex (PCC). CBF and 18F-FDG-PET showed abnormalities in similar areas, particularly in medial temporoparietal regions, consistent with the typically observed pattern of prodromal AD. The hypoperfusion pattern with relative CBF (obtained by normalizing voxel CBF values with mean CBF in putamen) was more localized than with absolute CBF. Pearson's correlation coefficients between the T-scores corresponding to the group-differences obtained with 18F-FDG-PET SUVR and absolute and relative ASL CBF were 0. 46 and 0. 43 (p<0. 001), respectively. ROI analyses were also consistent, with the strongest differences observed in PCC (p<0. 01). 18F-FDG-PET SUVR, absolute and relative CBF in the PCC ROI demonstrated moderate and similar discriminatory power in predicting MCI status with AUC of 0. 71 ± 0. 12, 0. 77 ± 0. 12 and 0. 74 ± 0. 13, respectively. In conclusion, ASL CBF may be a reasonable, less expensive and safer substitute for 18F-FDG-PET in clinical research.

YNIMG Journal 2020 Journal Article

Rotated spiral RARE for high spatial and temporal resolution volumetric arterial spin labeling acquisition

• Fanny Munsch
• Manuel Taso
• Li Zhao
• R. Marc Lebel
• Arnaud Guidon
• John A. Detre
• David C. Alsop

Background Arterial Spin Labeling (ASL) MRI can provide quantitative images that are sensitive to both time averaged blood flow and its temporal fluctuations. 3D image acquisitions for ASL are desirable because they are more readily compatible with background suppression to reduce noise, can reduce signal loss and distortion, and provide uniform flow sensitivity across the brain. However, single-shot 3D acquisition for maximal temporal resolution typically involves degradation of image quality through blurring or noise amplification by parallel imaging. Here, we report a new approach to accelerate a common stack of spirals 3D image acquisition by pseudo golden-angle rotation and compressed sensing reconstruction without any degradation of time averaged blood flow images. Methods 28 healthy volunteers were imaged at 3T with background-suppressed unbalanced pseudo-continuous ASL combined with a pseudo golden-angle Stack-of-Spirals 3D RARE readout. A fully-sampled perfusion-weighted volume was reconstructed by 3D non-uniform Fast Fourier Transform (nuFFT) followed by sum-of-squares combination of the 32 individual channels. Coil sensitivities were estimated followed by reconstruction of the 39 single-shot volumes using an L1-wavelet Compressed-Sensing reconstruction. Finally, brain connectivity analyses were performed in regions where BOLD signal suffers from low signal-to-noise ratio and susceptibility artifacts. Results Image quality, assessed with a non-reference 3D blurring metric, of full time averaged blood flow was comparable to a conventional interleaved acquisition. The temporal resolution provided by the acceleration enabled identification and quantification of resting-state networks even in inferior regions such as the amygdala and inferior frontal lobes, where susceptibility artifacts can degrade conventional resting-state fMRI acquisitions. Conclusion This approach can provide measures of blood flow modulations and resting-state networks for free within any research or clinical protocol employing ASL for resting blood flow.

YNICL Journal 2019 Journal Article

Characterizing a perfusion-based periventricular small vessel region of interest

• Sudipto Dolui
• Dylan Tisdall
• Marta Vidorreta
• David R. Jacobs
• Ilya M. Nasrallah
• R. Nick Bryan
• David A. Wolk
• John A. Detre

The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

YNIMG Journal 2019 Journal Article

Test-retest reliability of cerebral blood flow for assessing brain function at rest and during a vigilance task

• Fan Nils Yang
• Sihua Xu
• Andrea Spaeth
• Olga Galli
• Ke Zhao
• Zhuo Fang
• Mathias Basner
• David F. Dinges

Arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) is increasingly used to assess regional brain activity and cerebrovascular function in both healthy and clinical populations. ASL perfusion imaging provides a quantitative measure of regional brain activity by determining absolute cerebral blood flow (CBF) values at a resting state or during task performance. However, the comparative reliability of these ASL measures is not well characterized. It is also unclear whether the test-retest reliability of absolute CBF or task-induced CBF change measures would be comparable to the reliability of task performance. In this study, fifteen healthy participants were scanned three times in a strictly controlled in-laboratory study while at rest and during performing a simple and reliable psychomotor vigilance test (PVT). The reliability of absolute CBF and task-induced CBF changes was evaluated using the intraclass correlation coefficient (ICC) and compared to that of task performance. Absolute CBF showed excellent test-retest reliability across the three scans for both resting and PVT scans. The reliability of regional absolute CBF was comparable to that of behavioral measures of PVT performance, and was slightly higher during PVT scans as compared with resting scans. Task-induced regional CBF changes demonstrated only poor to moderate reliability across three scans. These findings suggest that absolute CBF measures are more reliable than task-induced CBF changes for characterizing regional brain function, especially for longitudinal and clinical studies.

YNIMG Journal 2018 Journal Article

Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI

• Zhengjun Li
• Marta Vidorreta
• Natalie Katchmar
• David C. Alsop
• Daniel H. Wolf
• John A. Detre

Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition.

YNIMG Journal 2017 Journal Article

Heterogeneous increases of regional cerebral blood flow during preterm brain development: Preliminary assessment with pseudo-continuous arterial spin labeled perfusion MRI

• Minhui Ouyang
• Peiying Liu
• Tina Jeon
• Lina Chalak
• Roy Heyne
• Nancy K. Rollins
• Daniel J. Licht
• John A. Detre

The human brain develops rapidly during 32-45 postmenstrual weeks (PMW), a critical stage characterized by dramatic increases of metabolic demand. The increasing metabolic demand can be inferred through measurements of regional cerebral blood flow (CBF), which might be coupled to regional metabolism in preterm brains. Arterial spin labeled (ASL) perfusion MRI is one of the few viable approaches for imaging regional CBF of preterm brains, but must be optimized for the extremely slow blood velocity unique in preterm brains. In this study, we explored the spatiotemporal CBF distribution in newborns scanned at the age of 32-45PMW using a pseudo-continuous ASL (pCASL) protocol adapted to slow blood flow in neonates. A total of 89 neonates were recruited. PCASL MRI was acquired from 34 normal newborns and phase contrast (PC) images from 19 newborns. Diffusion tensor images (DTI) were acquired from all 89 neonates for measuring cortical fractional anisotropy (FA), which characterizes cortical microstructure. Reproducible CBF measurements were obtained with the adjusted pCASL sequence. Global CBF measurement based on PC MRI was found to double its value in the 3rd trimester. Regional CBF increases were heterogeneous across the brain with a significantly higher rate of CBF increase in the frontal lobe and a lower rate of CBF increase in the occipital lobe. A significant correlation was found between frontal cortical CBF and cortical FA measurements (p<0. 01). Increasing CBF values observed in the frontal lobe corresponded to lower FA values, suggesting that dendritic arborization and synaptic formation might be associated with an elevated local CBF. These results offer a preliminary account of heterogeneous regional CBF increases in a vital early developmental period and may shed the light on underlying metabolic support for cortical microstructural changes during the developmental period of 32-45PMW. Preterm effects and limitations of pCASL techniques in newborns need to be carefully considered for interpretation these results.

YNICL Journal 2017 Journal Article

Prematurity and brain perfusion: Arterial spin labeling MRI

• Domenico Tortora
• Peter Angelo Mattei
• Riccardo Navarra
• Valentina Panara
• Rita Salomone
• Andrea Rossi
• John A. Detre
• Massimo Caulo

PURPOSE: Abnormal brain perfusion is a critical mechanism in neonatal brain injury. The aim of the present study was to compare Cerebral Blood Flow (CBF) evaluated with ASL MRI in three groups of neonates: preterms without brain lesions on MRI (PN), preterms with periventricular white matter lesions (PNp) and term neonates with normal MRI (TN). The correlation between CBF and clinical outcome was explored. MATERIALS AND METHODS: test. Logistic regression analysis was used to assess the relation between CBF and neuromotor outcome at 12 months. RESULTS: = 0.012). CONCLUSIONS: ASL MRI demonstrated differences in brain perfusion of the basal ganglia between PN and TN. In PN, a positive correlation between CBF and neuromotor outcome was demonstrated in this area.

YNICL Journal 2016 Journal Article

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment

• Long Xie
• Sudipto Dolui
• Sandhitsu R. Das
• Grace E. Stockbower
• Molly Daffner
• Hengyi Rao
• Paul A. Yushkevich
• John A. Detre

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

YNIMG Journal 2015 Journal Article

Decomposing cerebral blood flow MRI into functional and structural components: A non-local approach based on prediction

• Benjamin M. Kandel
• Danny J.J. Wang
• John A. Detre
• James C. Gee
• Brian B. Avants

We present RIPMMARC (Rotation Invariant Patch-based Multi-Modality Analysis aRChitecture), a flexible and widely applicable method for extracting information unique to a given modality from a multi-modal data set. We use RIPMMARC to improve the interpretation of arterial spin labeling (ASL) perfusion images by removing the component of perfusion that is predicted by the underlying anatomy. Using patch-based, rotation invariant descriptors derived from the anatomical image, we learn a predictive relationship between local neuroanatomical structure and the corresponding perfusion image. This relation allows us to produce an image of perfusion that would be predicted given only the underlying anatomy and a residual image that represents perfusion information that cannot be predicted by anatomical features. Our learned structural features are significantly better at predicting brain perfusion than tissue probability maps, which are the input to standard partial volume correction techniques. Studies in test–retest data show that both the anatomically predicted and residual perfusion signals are highly replicable for a given subject. In a pediatric population, both the raw perfusion and structurally predicted images are tightly linked to age throughout adolescence throughout the brain. Interestingly, the residual perfusion also shows a strong correlation with age in selected regions including the hippocampi (corr=0. 38, p-value <10−6), precuneus (corr=−0. 44, p <10−5), and combined default mode network regions (corr=−0. 45, p <10−8) that is independent of global anatomy-perfusion trends. This finding suggests that there is a regionally heterogeneous pattern of functional specialization that is distinct from that of cortical structural development.

YNIMG Journal 2014 Journal Article

In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy

• Rachelle Crescenzi
• Catherine Debrosse
• Ravi Prakash Reddy Nanga
• Sanjana Reddy
• Mohammed Haris
• Hari Hariharan
• Michiyo Iba
• Virginia M.Y. Lee

Glutamate is the primary excitatory neurotransmitter in the brain, and is implicated in neurodegenerative diseases such as Alzheimer's disease (AD) and several other tauopathies. The current method for measuring glutamate in vivo is proton magnetic resonance spectroscopy (1H MRS), although it has poor spatial resolution and weak sensitivity to glutamate changes. In this study, we sought to measure the effect of tau pathology on glutamate levels throughout the brain of a mouse model of tauopathy using a novel magnetic resonance imaging (MRI) technique. We employed glutamate chemical exchange saturation transfer (GluCEST) imaging, which has been previously validated as a complimentary method for measuring glutamate levels with several important advantages over conventional 1H MRS. We hypothesized that the regional changes in glutamate levels would correlate with histological measurements of pathology including pathological tau, synapse and neuron loss. Imaging and spectroscopy were carried out on tau transgenic mice with the P301S mutation (PS19, n =9) and their wild-type littermates (WT, n =8), followed by immunohistochemistry of their brain tissue. GluCEST imaging resolution allowed for sub-hippocampal analysis of glutamate. Glutamate was significantly decreased by 29% in the CA sub-region of the PS19 hippocampus, and by 15% in the thalamus, where synapse loss was also measured. Glutamate levels and synapse density remained high in the dentate gyrus sub-region of the hippocampus, where neurogenesis is known to occur. The further development of GluCEST imaging for preclinical applications will be valuable, as therapies are being tested in mouse models of tauopathy.

YNICL Journal 2013 Journal Article

Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study

• Ze Wang
• Sandhitsu R. Das
• Sharon X. Xie
• Steven E. Arnold
• John A. Detre
• David A. Wolk

We examined differences in cerebral blood flow (CBF) measured by Arterial Spin Labeled perfusion MRI (ASL MRI) across the continuum from cognitively normal (CN) older adults to mild Alzheimer's Disease (AD) using data from the multi-site Alzheimer's Disease Neuroimaging Initiative (ADNI). Measures of CBF, in a predetermined set of regions (meta-ROI), and hippocampal volume were compared between CN (n = 47), patients with early and late Mild Cognitive Impairment [EMCI (n = 32), LMCI (n = 35)], and AD (n = 15). Associations between these measures and disease severity, assessed by Clinical Dementia Rating scale sum of boxes (CDR SB), were also assessed. Mean meta-ROI CBF was associated with group status and significant hypoperfusion was observed in LMCI and AD relative to CN. Hippocampal volume was associated with group status, but only AD patients had significantly smaller volumes than the CN. When examining the relationship between these measures and disease severity, both were significantly associated with CDR SB and appeared to provide independent prediction of status. In light of the tight link between CBF and metabolism, ASL MRI represents a promising functional biomarker for early diagnosis and disease tracking in AD and this study is the first to demonstrate the feasibility in a multi-site context in this population. Combining functional and structural measures, which can be acquired in the same scanning session, appears to provide additional information about disease severity relative to either measure alone.

YNIMG Journal 2013 Journal Article

Comparison of 2D and 3D single-shot ASL perfusion fMRI sequences

• Marta Vidorreta
• Ze Wang
• Ignacio Rodríguez
• María A. Pastor
• John A. Detre
• María A. Fernández-Seara

Arterial spin labeling (ASL) can be implemented by combining different labeling schemes and readout sequences. In this study, the performance of 2D and 3D single-shot pulsed-continuous ASL (pCASL) sequences was assessed in a group of young healthy volunteers undergoing a baseline perfusion and a functional study with a sensory-motor activation paradigm. The evaluated sequences were 2D echo-planar imaging (2D EPI), 3D single-shot fast spin-echo with in-plane spiral readout (3D FSE spiral), and 3D single-shot gradient-and-spin-echo (3D GRASE). The 3D sequences were implemented with and without the addition of an optimized background suppression (BS) scheme. Labeling efficiency, signal-to-noise ratio (SNR), and gray matter (GM) to white matter (WM) contrast ratio were assessed in baseline perfusion measurements. 3D acquisitions without BS yielded 2-fold increments in spatial SNR, but no change in temporal SNR. The addition of BS to the 3D sequences yielded a 3-fold temporal SNR increase compared to the unsuppressed sequences. 2D EPI provided better GM-to-WM contrast ratio than the 3D sequences. The analysis of functional data at the subject level showed a 3-fold increase in statistical power for the BS 3D sequences, although the improvement was attenuated at the group level. 3D without BS did not increase the maximum t-values, however, it yielded larger activation clusters than 2D. These results demonstrate that BS 3D single-shot imaging sequences improve the performance of pCASL in baseline and activation studies, particularly for individual subject analyses where the improvement in temporal SNR translates into markedly enhanced power for task activation detection.

YNIMG Journal 2013 Journal Article

Direct visualization of short transverse relaxation time component (ViSTa)

• Se-Hong Oh
• Michel Bilello
• Matthew Schindler
• Clyde E. Markowitz
• John A. Detre
• Jongho Lee

White matter of the brain has been demonstrated to have multiple relaxation components. Among them, the short transverse relaxation time component (T2 <40ms; T2 ⁎ <25ms at 3T) has been suggested to originate from myelin water whereas long transverse relaxation time components have been associated with axonal and/or interstitial water. In myelin water imaging, T2 or T2 ⁎ signal decay is measured to estimate myelin water fraction based on T2 or T2 ⁎ differences among the water components. This method has been demonstrated to be sensitive to demyelination in the brain but suffers from low SNR and image artifacts originating from ill-conditioned multi-exponential fitting. In this study, a novel approach that selectively acquires short transverse relaxation time signal is proposed. The method utilizes a double inversion RF pair to suppress a range of long T1 signal. This suppression leaves short T2 ⁎ signal, which has been suggested to have short T1, as the primary source of the image. The experimental results confirm that after suppression of long T1 signals, the image is dominated by short T2 ⁎ in the range of myelin water, allowing us to directly visualize the short transverse relaxation time component in the brain. Compared to conventional myelin water imaging, this new method of direct visualization of short relaxation time component (ViSTa) provides high quality images. When applied to multiple sclerosis patients, chronic lesions show significantly reduced signal intensity in ViSTa images suggesting sensitivity to demyelination.

YNIMG Journal 2012 Journal Article

The development and future of perfusion fMRI for dynamic imaging of human brain activity

• Geoffrey K. Aguirre
• John A. Detre

Arterial spin labeled (ASL), perfusion fMRI was developed nearly simultaneously with BOLD fMRI. The application of this technique in studies of human brain activity has grown slowly over the last twenty years, primarily because of the need to meet technical challenges in data acquisition and analysis. Even within these constraints, perfusion fMRI has been identified as a tool that is well suited to measure slow changes in neural activity and to examine individual differences in brain–behavior relationships. Major advances have been made in acquisition and analysis techniques during this time. With further, anticipated technical improvements, perfusion fMRI studies in humans are poised to gain the improved cortical spatial resolution that has been observed in animal studies. If achieved, these advances portend surprising future applications of perfusion fMRI, including multi-voxel pattern analysis.

YNIMG Journal 2011 Journal Article

Heterogeneity of functional activation during memory encoding across hippocampal subfields in temporal lobe epilepsy

• Sandhitsu R. Das
• Dawn Mechanic-Hamilton
• John Pluta
• Marc Korczykowski
• John A. Detre
• Paul A. Yushkevich

Pathology studies have shown that the anatomical subregions of the hippocampal formation are differentially affected in various neurological disorders, including temporal lobe epilepsy (TLE). Analysis of structure and function within these subregions using magnetic resonance imaging (MRI) has the potential to generate insights on disease associations as well as normative brain function. In this study, an atlas-based normalization method (Yushkevich, P. A. , Avants, B. B. , Pluta, J. , Das, S. , Minkoff, D. , Mechanic-Hamilton, D. , Glynn, S. , Pickup, S. , Liu, W. , Gee, J. C. , Grossman, M. , Detre, J. A. , 2009. A high-resolution computational atlas of the human hippocampus from postmortem magnetic resonance imaging at 9. 4 T. NeuroImage 44 (2), 385–398) was used to label hippocampal subregions, making it possible to examine subfield-level functional activation during an episodic memory task in two different cohorts of healthy controls and subjects diagnosed with intractable unilateral TLE. We report, for the first time, functional activation patterns within hippocampal subfields in TLE. We detected group differences in subfield activation between patients and controls as well as inter-hemispheric activation asymmetry within subfields in patients, with dentate gyrus (DG) and the anterior hippocampus region showing the greatest effects. DG was also found to be more active than CA1 in controls, but not in patients’ epileptogenic side. These preliminary results will encourage further research on the utility of subfield-based biomarkers in TLE.

YNIMG Journal 2010 Journal Article

Early parental care is important for hippocampal maturation: Evidence from brain morphology in humans

• Hengyi Rao
• Laura Betancourt
• Joan M. Giannetta
• Nancy L. Brodsky
• Marc Korczykowski
• Brian B. Avants
• James C. Gee
• Jiongjiong Wang

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

YNIMG Journal 2010 Journal Article

Imaging brain fatigue from sustained mental workload: An ASL perfusion study of the time-on-task effect

• Julian Lim
• Wen-Chau Wu
• Jiongjiong Wang
• John A. Detre
• David F. Dinges
• Hengyi Rao

During sustained periods of a taxing cognitive workload, humans typically display time-on-task (TOT) effects, in which performance gets steadily worse over the period of task engagement. Arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) was used in this study to investigate the neural correlates of TOT effects in a group of 15 subjects as they performed a 20-min continuous psychomotor vigilance test (PVT). Subjects displayed significant TOT effects, as seen in progressively slower reaction times and significantly increased mental fatigue ratings after the task. Perfusion data showed that the PVT activates a right lateralized fronto-parietal attentional network in addition to the basal ganglia and sensorimotor cortices. The fronto-parietal network was less active during post-task rest compared to pre-task rest, and regional CBF decrease in this network correlated with performance decline. These results demonstrate the persistent effects of cognitive fatigue in the fronto-parietal network after a period of heavy mental work and indicate the critical role of this attentional network in mediating TOT effects. Furthermore, resting regional CBF in the thalamus and right middle frontal gyrus prior to task onset was predictive of subjects' subsequent performance decline, suggesting that resting CBF quantified by ASL perfusion fMRI may be a useful indicator of performance potential and a marker of the level of fatigue in the neural attentional system.

YNIMG Journal 2009 Journal Article

Function lateralization via measuring coherence laterality

• Ze Wang
• Dawn Mechanic-Hamilton
• John Pluta
• Simon Glynn
• John A. Detre

A data-driven approach for lateralization of brain function based on the spatial coherence difference of functional MRI (fMRI) data in homologous regions-of-interest (ROI) in each hemisphere is proposed. The utility of using coherence laterality (CL) to determine function laterality was assessed first by examining motor laterality using normal subjects' data acquired both at rest and with a simple unilateral motor task and subsequently by examining mesial temporal lobe memory laterality in normal subjects and patients with temporal lobe epilepsy. The motor task was used to demonstrate that CL within motor ROI correctly lateralized functional stimulation. In patients with unilateral epilepsy studied during a scene-encoding task, CL in a hippocampus–parahippocampus–fusiform (HPF) ROI was concordant with lateralization based on task activation, and the CL index (CLI) significantly differentiated the right side group to the left side group. By contrast, normal controls showed a symmetric HPF CLI distribution. Additionally, similar memory laterality prediction results were still observed using CL in epilepsy patients with unilateral seizures after the memory encoding effect was removed from the data, suggesting the potential for lateralization of pathological brain function based on resting fMRI data. A better lateralization was further achieved via a combination of the proposed approach and the standard activation based approach, demonstrating that assessment of spatial coherence changes provides a complementary approach to quantifying task-correlated activity for lateralizing brain function.

YNIMG Journal 2008 Journal Article

Assessment of functional development in normal infant brain using arterial spin labeled perfusion MRI

• Ze Wang
• María Fernández-Seara
• David C. Alsop
• Wen-Ching Liu
• Judy F. Flax
• April A. Benasich
• John A. Detre

Arterial spin labeled (ASL) perfusion MRI provides a noninvasive approach for longitudinal imaging of regional brain function in infants. In the present study, continuous ASL (CASL) perfusion MRI was carried out in normally developing 7- and 13-month-old infants while asleep without sedation. The 13-month infant group showed an increase (P <0. 05) of relative CBF in frontal regions as compared to the 7-month group using a region of interest based analysis. Using a machine-learning algorithm to automatically classify the relative CBF maps of the two infant groups, a significant (P <0. 05, permutation testing) regional CBF increase was found in the hippocampi, anterior cingulate, amygdalae, occipital lobes, and auditory cortex in the 13-month-old infants. These results are consistent with current understanding of infant brain development and demonstrate the feasibility of using perfusion MRI to noninvasively monitor developing brain function.

YNIMG Journal 2008 Journal Article

Narrative speech production: An fMRI study using continuous arterial spin labeling

• Vanessa Troiani
• Maria A. Fernández-Seara
• Ze Wang
• John A. Detre
• Sherry Ash
• Murray Grossman

Functional magnetic resonance imaging (fMRI) with continuous arterial spin labeling (CASL) was employed to monitor brain activation during narrative production of a semi-structured speech sample in healthy young adults. Subjects were asked to describe a wordless children’s picture story. Significant activations were found in bilateral prefrontal and left temporal–parietal regions during narrative production relative to description of a single picture and relative to viewing the wordless picture story while producing a nonsense word. We conclude that inferior frontal cortex serves as a top–down organizational resource for narrative production and demonstrate the feasibility of collecting extended speech samples using CASL perfusion fMRI.

YNIMG Journal 2008 Journal Article

Neural correlates of voluntary and involuntary risk taking in the human brain: An fMRI Study of the Balloon Analog Risk Task (BART)

• Hengyi Rao
• Marc Korczykowski
• John Pluta
• Angela Hoang
• John A. Detre

Increasing effort has been devoted to understanding the neural mechanisms underlying decision making during risk, yet little is known about the effect of voluntary choice on risk taking. The Balloon Analog Risk Task (BART), in which subjects inflate a virtual balloon that can either grow larger or explode [Lejuez, C. W. , Read, J. P. , Kahler, C. W. , Richards, J. B. , Ramsey, S. E. , Stuart, G. L. , Strong, D. R. , Brown, R. A. , 2002. Evaluation of a behavioral measure of risk taking: the Balloon Analogue Risk Task BART. J. Exp. Psychol. Appl. 8, 75–84. ], provides an ecologically valid model to assess human risk taking propensity and behaviour. In the present study, we modified this task for use during functional magnetic resonance imaging (fMRI) and administered it in both an active choice mode and a passive no-choice mode in order to examine the neural correlates of voluntary and involuntary risk taking in the human brain. Voluntary risk in the active choice task is associated with robust activation in mesolimbic-frontal regions, including the midbrain, ventral and dorsal striatum, anterior insula, dorsal lateral prefrontal cortex (DLPFC), and anterior cingulate/medial frontal cortex (ACC/MFC), in addition to activation in visual pathway regions. However, these mesolimbic-frontal activation patterns were not observed for involuntary risk in the passive no-choice task. Decision making was associated with neural activity in the right DLPFC. These findings demonstrate the utility of the modified BART paradigms for using during fMRI to assess risk taking in the human brain, and suggest that recruitment of the brain mesolimbic-frontal pathway during risk-taking is contingent upon the agency of the risk taker. The present paradigm may be extended to pathological populations to determine the specific neural components of their impaired risk behavior.

YNIMG Journal 2008 Journal Article

Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study

• Junghoon Kim
• Brian Avants
• Sunil Patel
• John Whyte
• Branch H. Coslett
• John Pluta
• John A. Detre
• James C. Gee

Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume >1. 5 cm3). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain–behavior relationships in the TBI population.

YNIMG Journal 2007 Journal Article

Hippocampus-specific fMRI group activation analysis using the continuous medial representation

• Paul A. Yushkevich
• John A. Detre
• Dawn Mechanic-Hamilton
• María A. Fernández-Seara
• Kathy Z. Tang
• Angela Hoang
• Marc Korczykowski
• Hui Zhang

We present a new shape-based approach for regional group activation analysis in fMRI studies. The method restricts anatomical normalization, spatial smoothing and random effects statistical analysis to the space inside and around a structure of interest. Normalization involves finding intersubject correspondences between manually outlined masks, and it leverages the continuous medial representation, which makes it possible to extend surface-based shape correspondences to the space inside and outside of structures. Our approach is an alternative to whole-brain normalization in cases where the latter may fail due to anatomical variability or pathology. It also provides an opportunity to analyze the shape and thickness of structures concurrently with functional activation. We apply the technique to the hippocampus and evaluate it using data from a visual scene encoding fMRI study, where activation in the hippocampus is expected. We produce detailed statistical maps of hippocampal activation, as well as maps comparing activation inside and outside of the hippocampus. We find that random effects statistics computed by the new approach are more significant than those produced using the Statistical Parametric Mapping framework (Friston, K. J. , Holmes, A. P. , Worsley, K. J. , Poline, J. -P. , Firth, C. D. , Frackowiak, R. S. J. 1994, Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping, 2(4): 189–210) at low levels of smoothing, suggesting that greater specificity can be achieved by the new method without a severe tradeoff in sensitivity.

YNIMG Journal 2007 Journal Article

Support vector machine learning-based fMRI data group analysis

• Ze Wang
• Anna R. Childress
• Jiongjiong Wang
• John A. Detre

To explore the multivariate nature of fMRI data and to consider the inter-subject brain response discrepancies, a multivariate and brain response model-free method is fundamentally required. Two such methods are presented in this paper by integrating a machine learning algorithm, the support vector machine (SVM), and the random effect model. Without any brain response modeling, SVM was used to extract a whole brain spatial discriminance map (SDM), representing the brain response difference between the contrasted experimental conditions. Population inference was then obtained through the random effect analysis (RFX) or permutation testing (PMU) on the individual subjects' SDMs. Applied to arterial spin labeling (ASL) perfusion fMRI data, SDM RFX yielded lower false-positive rates in the null hypothesis test and higher detection sensitivity for synthetic activations with varying cluster size and activation strengths, compared to the univariate general linear model (GLM)-based RFX. For a sensory–motor ASL fMRI study, both SDM RFX and SDM PMU yielded similar activation patterns to GLM RFX and GLM PMU, respectively, but with higher t values and cluster extensions at the same significance level. Capitalizing on the absence of temporal noise correlation in ASL data, this study also incorporated PMU in the individual-level GLM and SVM analyses accompanied by group-level analysis through RFX or group-level PMU. Providing inferences on the probability of being activated or deactivated at each voxel, these individual-level PMU-based group analysis methods can be used to threshold the analysis results of GLM RFX, SDM RFX or SDM PMU.

YNIMG Journal 2006 Journal Article

Continuous ASL perfusion fMRI investigation of higher cognition: Quantification of tonic CBF changes during sustained attention and working memory tasks

• Junghoon Kim
• John Whyte
• Jiongjiong Wang
• Hengyi Rao
• Kathy Z. Tang
• John A. Detre

Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6–12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7–11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow.

YNIMG Journal 2005 Journal Article

Concurrent CBF and CMRGlc changes during human brain activation by combined fMRI–PET scanning

• Andrew B. Newberg
• Jiongjiong Wang
• Hengyi Rao
• Randel L. Swanson
• Nancy Wintering
• Joel S. Karp
• Abass Alavi
• Joel H. Greenberg

A novel approach for concurrent measurement of regional cerebral blood flow (CBF) and regional cerebral metabolic rate for glucose consumption (CMRGlc) in humans is proposed and validated in normal subjects during visual stimulation. 18F-labeled fluorodeoxyglucose was administered during the measurement of CBF by continuous arterial spin labeled magnetic resonance imaging (MRI). Subsequent positron emission tomographic (PET) scanning demonstrated the distribution of labeled deoxyglucose during the MRI acquisition. An excellent concordance between regional CBF and regional CMRGlc during visual stimulation was found, consistent with previously published PET findings. Although initially validated using a brief, non-quantitative protocol, this approach can provide quantitative CBF and CMRGlc, with a broad range of potential applications in functional physiology and pathophysiology.

YNIMG Journal 2003 Journal Article

Temporal Dynamics of Brain Tissue Nitric Oxide during Functional Forepaw Stimulation in Rats

• Donald G. Buerk
• Beau M. Ances
• Joel H. Greenberg
• John A. Detre

We report the first dynamic measurements of tissue nitric oxide (NO) during functional activation of rat somatosensory cortex by electrical forepaw stimulation. Cortical tissue NO was measured electrochemically with rapid-responding recessed microelectrodes (tips <10 μm). Simultaneous blood flow measurements were made by laser–Doppler flowmetry (LDF). NO immediately increased, reaching a peak 125. 5 ± 32. 8 (SE) nM above baseline (P < 0. 05) within 400 ms after stimulus onset, preceding any LDF changes, and then returned close to prestimulus levels after 2 s (123 signal-averaged trials, 12 rats). Blood flow began rising after a 1-s delay, reaching a peak just before electrical stimulation was ended at t = 4 s. A consistent poststimulus NO undershoot was observed as LDF returned to baseline. These findings complement our previous study (B. M. Ances et al. , 2001, Neurosci. Lett. 306, 106–110) in which a transient decrease in rat somatosensory cortex tissue oxygen partial pressure was found to precede blood flow increases during functional activation.

YNIMG Journal 2000 Journal Article

Hemispheric effects of frontal lobe tumors on mesial temporal lobe activation during scene encoding

• Faez Siddiqi
• Daniel J. Casasanto
• John A. Detre
• Guila Glosser
• David C. Alsop
• Joseph A. Maldjian

YNIMG Journal 2000 Journal Article

Neural correlates of successful and unsuccessful verbal encoding

• Daniel J. Casasanto
• William D. Scott Killgore
• Joseph A. Maldjian
• Guila Glosser
• Murray Grossman
• David C. Alsop
• John A. Detre

YNIMG Journal 2000 Journal Article

Strategy for enhancement of the early negativity in the BOLD fMRI response using short inter-stimulus intervals

• Beau Ances
• John A. Detre

YNIMG Journal 2000 Journal Article

Temporal dynamics of the brain oxygen metabolism during functional activation using laser doppler and oxygen-dependent phosphorescence quenching

• Beau M. Ances
• David F. Wilson
• Joel H. Greenberg
• John A. Detre

YNIMG Journal 1999 Journal Article

Laser Doppler Imaging of Activation-Flow Coupling in the Rat Somatosensory Cortex

• Beau M. Ances
• Joel H. Greenberg
• John A. Detre

Activation-flow coupling (AFC) provides a physiological basis for mapping cerebral activation using cerebral blood flow (CBF) as a surrogate marker for neuronal function. Laser Doppler offers a minimally invasive approach for measuring changes in cerebral blood flow but the spatial resolution of this technique is limited by the number of individual probes that can be used. Recently, laser Doppler imaging (LDI) scanners, which use computer-driven optics to scan and measure LD changes in two dimensions, have successfully measured flow changes in the exposed cortex of animals. Here we demonstrate the use of an LDI device through a thinned skull to determine the spatiotemporal characteristics of AFC in α-chloralose anesthetized rats in response to electrical forepaw stimulation. The spatial and temporal characteristics of the AFC response measured by LDI are in agreement with prior results obtained using a single LD probe. These results suggest a promising role for LDI in the characterization of the spatiotemporal characteristics of AFC in animal models and possibly for intraoperative monitoring in the human brain.

YNIMG Journal 1999 Journal Article

The Sensory Somatotopic Map of the Human Hand Demonstrated at 4 Tesla

• Joseph A. Maldjian
• Allan Gottschalk
• Rita S. Patel
• John A. Detre
• David C. Alsop

Recent attempts at high-resolution sensory-stimulated fMRI performed at 1. 5 T have had very limited success at demonstrating a somatotopic organization for individual digits. Our purpose was to determine if functional MRI at 4 T can demonstrate the sensory somatotopic map of the human hand. Sensory functional MRI was performed at 4 T in five normal volunteers using a low-frequency vibratory stimulus on the pad of each finger of the left hand. A simple motor control task was also performed. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were computed for each task. Volume of activation and distribution of cluster maxima were compared for each task. For three of the subjects, the SPMs demonstrated a somatotopic organization of the sensory cortex. The group SPMs demonstrated a clear somatotopic organization of the sensory cortex. The thumb to fifth finger were organized, in general, with a lateral to medial, inferior to superior, and anterior to posterior relationship. There was overlap in the individual SPMs between fingers. The sensory activation spanned a space of 12–18 mm (thumb to fifth finger) on the primary sensory cortex. The motor activation occurred consistently at the superior-most extent of the sensory activation within and across subjects. The sensory somatotopic map of the human hand can be identified at 4 T. High-resolution imaging at 4 T can be useful for detailed functional imaging studies.