Dr.
Hua’s research has centered on the development of novel MRI technologies
for in vivo functional and physiological imaging in the brain, and
the application of such methods for studies in healthy and diseased brains.
These include the development of human and animal MRI methods to measure
functional brain activities, cerebral perfusion and oxygen metabolism at
high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is
particularly interested in novel MRI approaches to image small blood and
lymphatic vessels in the brain. Collaborating with clinical investigators, these
techniques have been applied 1) to detect functional, vascular and
metabolic abnormalities in the brain in neurodegenerative diseases such as
Huntingdon’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease
(AD) and mental disorders such as schizophrenia; and 2) to map brain
functions and cerebrovascular reactivity for presurgical planning in
patients with vascular malformations, brain tumors and epilepsy.
Imaging
technology development
1)
Inflow-based
vascular space occupancy (iVASO) MRI
In the brain, the supply of adequate oxygen and energy
substrates for local metabolic demands is controlled by blood vessels.
Therefore, microvascular abnormalities often accompany metabolic
disturbance in the brain, and have been associated with many neurodegenerative
diseases. To date, most studies of the microvasculature in the brain using
MRI measure total cerebral blood volume (CBV) and flow (CBF) in the brain,
which reflects the sum of signals from the arterial and venous vessels in
the microvasculature. However, different types of blood vessels have
distinct functions and physiology, and can be affected differentially by
pathology. The arterioles are the most actively regulated blood vessels,
and thus may be more sensitive to metabolic disturbances in the brain. Therefore,
the measurement of changes in each type of blood vessels in different
segments of the microvasculature separately may furnish information that is
not obtainable from total CBV and CBF measures, and may provide a more
sensitive biomarker for brain diseases. The inflow-based vascular space
occupancy (iVASO) MRI approach was developed in our group, which can
measure CBV in small pial arteries and arterioles (CBVa) with
diameters up to 100-150 microns. Unlike many existing MRI methods for CBV
measurements, this is a truly non-invasive method, which does not require
the administration of exogenous contrast agents. The iVASO method has been applied
in several brain diseases such as stroke, brain tumors, Huntington’s
disease, Alzheimer’s disease, Parkinson’s disease, and schizophrenia.
Figures from Hua et al., NMR in Biomedicine
24(10):1313-25, 2011.
Selected publications:
1)
Hua J, Qin Q, Donahue MJ, Zhou J, Pekar JJ,
Van Zijl PCM. Inflow-based Vascular Space Occupancy (VASO) MRI. Magnetic
Resonance in Medicine 66:40-56, 2011. PMC3121008.
2)
Hua J, Qin Q, Pekar JJ, Van Zijl PCM.
Measurement of absolute arterial cerebral blood volume in human brain
without using a contrast agent. NMR in Biomedicine 24(10):1313-25, 2011.
PMC3192228.
3)
Hua J, Unschuld PG, Margolis RL, Van Zijl
PCM, Ross CA. Elevated Arteriolar Cerebral Blood Volume in Prodromal
Huntington’s Disease Patients. Movement Disorders 29(3):396-401 2014.
PMC3834086.
4)
Hua J, Brandt AS, Lee S, Blair NIS, Wu Y,
Su L, Patel J, Faria AV, Lim IAL, Unschuld PG, Pekar JJ, Van Zijl PCM,
Ross CA, Margolis RL. Abnormal Grey Matter Arteriolar Cerebral Blood Volume
in Schizophrenia Measured With 3D Inflow-Based Vascular-Space-Occupancy MRI
at 7T. Schizophrenia Bulletin, 2017 May 1;43(3):620-632. doi:10.1093/schbul/sbw109.
PMC5464028.
5)
Hua J, Lee S, Blair NIS, Wyss M, van
Bergen JMG, Schreiner SJ, Kagerer SM, Leh SE, Gietl AF, Treyer V, Buck A,
Nitsch RM, Pruessmann KP, Lu H, Van Zijl PCM, Albert M, Hock C, Unschuld
PG. Increased cerebral blood volume in small arterial vessels is a
correlate of amyloid-β-related cognitive decline. Neurobiol Aging
76:181-193, 2019 Jan. PMID: 30738323. PMC6438210.
6)
Hua J, Liu P, Kim T, Donahue M, Rane S,
Chen JJ, Qin Q, Kim SG. MRI techniques to measure arterial and venous cerebral
blood volume. Neuroimage 187:17-31, 2019. PMID: 29458187.
PMC6095829.
7)
Liu H, Chuangchuang Zhang, Jiadi Xu, Jing
Jin, Liam Cheng, Xinyuan Miao, Qian Wu, Zhiliang Wei, Peiying Liu, Hanzhang
Lu, Peter C. M. van Zijl, Christopher A. Ross, Hua J*, Wenzhen Duan*.
Huntingtin silencing delays onset and slows progression of Huntington’s
disease: a biomarker study. Brain. 2021 May 27;awab190. DOI:
10.1093/brain/awab190. PMID: 34043007.
2.
T2-prepared
(T2prep) BOLD fMRI and Diffusion-prepared DTI
Blood-oxygenation-level-dependent
(BOLD) functional MRI (fMRI) has revolutionized the noninvasive assessment
of brain function. Diffusion tensor imaging (DTI) is the only noninvasive
imaging method that can visualize the trajectories of main white matter (WM)
fascicles in vivo. Echo-planar-imaging (EPI) is currently the method of
choice for most fMRI and DTI studies. However, the well-known geometric
distortion and signal dropouts in EPI images caused by large magnetic
susceptibility effects have hampered its application in some areas. In a
normal brain, regions close to the skull base and paranasal sinuses at
bone/soft tissue and bone/air interfaces are usually most affected by these
susceptibility artifacts, which typically include the orbitofrontal regions
and temporal lobes.
Figure: Pulse
sequence diagram.
A
whole-brain T2-prepared (T2prep) BOLD fMRI approach was developed in our
group, which uses a spin preparation module (T2prep) before readout to
induce T2-weighted BOLD effects for fMRI. Similarly, the diffusion
sensitized driven equilibrium (DSDE) sequence was used for
diffusion-prepared DTI. By adopting a 3D fast GRE readout with short TE, a
sequence typically used in anatomical imaging, both sequences showed
minimal distortion and dropout across the entire brain, which provided
clear access to regions near air-filled cavities that are often
inaccessible with conventional EPI readout due to susceptibility artifacts.
Figure: Typical
images acquired using T2prep BOLD and GRE EPI (a) in a healthy brain, and
(b) in a subject wearing dental braces.
Metallic implants
Furthermore,
such susceptibility artifacts become more severe in the presence of MR
compatible metal head implants, such as metallic dental fillings and braces
and various other devices (MR compatible aneurysm clips, endovascular
coils, etc.). We performed T2prep BOLD fMRI and diffusion-prepared DTI in
healthy subjects wearing metallic dental braces to evaluate their ability
to minimize susceptibility artifacts in the presence of metallic objects.
Dental fillings and braces is particularly a problem for MRI studies
involving teenagers as >80% teenagers in the US and 33% of the world’s
population including adults have orthodontic treatments (www.aaoinfo.org). We
demonstrated that T2prep BOLD fMRI and diffusion-prepared DTI can acquire
functional and diffusion MR images, respectively, in healthy human subjects
wearing metallic dental braces without the susceptibility artifacts
commonly seen in conventional EPI images.
Figure from Miao
et al., Radiology. 2020 Jan;294(1):149-157
Presurgical brain mapping
Presurgical
brain mapping using fMRI and DTI have been increasingly performed in large
medical centers across the world. Presurgical functional mapping is
currently the most prevalent clinical application of fMRI and is the only
application of fMRI for which there are approved AMA (American Medical
Association) billing CPT (Current Procedural Terminology) codes
(http://www.asfnr.org/cpt-codes/). Presurgical fMRI is commonly used to
noninvasively locate essential cortical sensorimotor and language areas and
to determine the language dominant hemisphere prior to surgery, thus
helping to reduce the need for invasive diagnostic procedures such as
direct cortical stimulation and to provide complementary information. DTI
furnishes essential anatomical information on specific white matter
fascicles, and in the current era is an integral part of presurgical MRI.
The ultimate goal of surgery is to achieve maximal removal of the pathology
while preserving vital brain functions. To this end, preoperative fMRI and DTI
can provide indispensable information for neurosurgeons for the planning of
optimal treatment strategy on an individual basis.
A
significant subpopulation of patients who need to undergo presurgical brain
mapping are affected by the geometric distortion and signal dropout in
regions with large magnetic susceptibility effects when using the current
standard EPI based sequences. These include several regions near the skull
base and air cavities such as the orbitofrontal and temporal cortex that
are important for many cognitive and language functions, and brain areas
close to MR- compatible metallic head implants. Furthermore, such
susceptibility artifacts can also arise from cavities related to previous
surgery, calcified structures, hemorrhage, and metal implants.
Using
T2prep BOLD fMRI for presurgical mapping in epilepsy and brain tumor
patients, it showed greater functional sensitivity around the lesions
containing blood products and air-filled cavities compared to GRE EPI BOLD
fMRI. Functional activation was detected with T2prep BOLD but not GRE EPI
BOLD in the affected areas with the same functional tasks and statistical
threshold.
Figure from Hua
et al., Tomography 2017 Jun;3(2):105-113. Presurgical brain mapping
using fMRI in a patient with epilepsy with a large cavernous malformation
in the left temporal lobe and a small one in the anterior left frontal
lobe, causing signal dropouts in the areas in the EPI images (C). A
sentence completion task was performed for language mapping. Activation in
the left inferior frontal lobe (an important language region, yellow arrow)
was detected in the T2prep BOLD scan (A) but not the GRE EPI BOLD scan (C).
Olfactory fMRI
The
olfactory bulb and several other regions associated with olfaction such as
the piriform cortex (primary olfactory cortex) and orbitofrontal cortex are
substantially affected by the susceptibility artifacts caused by the nearby
nasal cavity. Using T2prep BOLD fMRI, functional activities can be detected
in these regions including the olfactory bulb, which is inaccessible with
conventional EPI sequences.
Figure: High
resolution (0.5mm) structural images showing regions related to the
olfactory system in the human brain.
Figure: A
custom-built multi-channel computer-controlled olfactometer used to deliver
the odorants in precisely timed pulses during fMRI scans.
Selected publications:
1)
Hua J, Qin Q, Van Zijl PCM, Pekar JJ, Jones
CK. Whole-brain three-dimensional T2-weighted BOLD functional magnetic
resonance imaging at 7 Tesla. Magnetic Resonance in Medicine 2014
Dec;72(6):1530-40. PMC4055555.
2)
Hua J, Miao X, Agarwal S, Bettegowda C,
Quiñones-Hinojosa A, Laterra J, Van Zijl PCM, Pekar JJ, Pillai JJ. Language
mapping using T2-prepared BOLD functional MRI in the presence of large
susceptibility artifacts – initial results in brain tumor and epilepsy
patients. Tomography 2017 Jun;3(2):105-113. DOI:
10.18383/j.tom.2017.00006. PMC5552052.
3)
Miao X, Wu Y, Liu D, Jiang H, Woods D,
Stern MT, Blair NIS, Airan RD, Bettegowda C, Rosch KS, Qin Q, van Zijl PCM,
Pillai JJ, Hua J*. Whole-Brain Functional and Diffusion Tensor MRI
in Human Participants with Metallic Orthodontic Braces. Radiology. 2020
Jan;294(1):149-157. doi: 10.1148/radiol.2019190070. Epub 2019 Nov 12.
PubMed PMID: 31714192; PubMed Central PMCID: PMC6939835.
4)
Miao X, Paez AG, Rajan S, Cao D, Liu D,
Pantelyat AY, Rosenthal LI, van Zijl PCM, Bassett SS, Yousem DM, Kamath V, Hua
J*. Functional Activities Detected in the Olfactory Bulb and Associated
Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI
at 7T. Front Neurosci. 2021;15:723441. doi: 10.3389/fnins.2021.723441.
eCollection 2021. PubMed PMID: 34588949; PubMed Central PMCID: PMC8476065.
3.
3D-TRIP
MRI
The
gross signal change in BOLD fMRI does not have a clear physiological
meaning. In fact, it may reflect an ensemble of changes in several
physiological parameters, including cerebral blood volume (CBV) and flow
(CBF), and cerebral metabolic rate of oxygen (CMRO2). A number of
approaches have been developed to measure CBV and/or CBF responses along
with the BOLD signal change, making it possible to calculate CMRO2 dynamics
using quantitative BOLD theories. Conventionally, BOLD, CBV, and CBF signal
changes are measured using consecutive MRI scans. In such approaches, the
scan time is relatively long, and more importantly, there may be changes in
physiological parameters between scans, causing inaccurate calculations of
CMRO2. The 3D-TRiple-acquisitionafter-Inversion-Preparation (3D-TRIP) MRI
approach was developed by our group, which can measure BOLD, CBF, and CBV
signal changes in a single MRI scan with whole brain coverage. Using this
approach, we were able to examine neurovascular and metabolic abnormalities
in the brain in several brain diseases, such as Huntington’s disease (HD)
and schizophrenia.
Figure: 3D-TRIP
MRI in a healthy human subject.
Selected publications:
1)
Cheng
Y, Van Zijl
PCM, Pekar JJ, Hua J*. Three-dimensional Acquisition of
Cerebral Blood Volume and Flow Responses during Functional Stimulation in a
Single Scan. Neuroimage 2014 Dec;103:533-41. PMC4252776.
2)
Cheng
Y, Qin Q,
Van Zijl PCM, Pekar JJ,
Hua J*. A three-dimensional single-scan
approach for the measurement of changes in cerebral blood volume, blood
flow, and blood oxygenation-weighted signals during functional stimulation.
Neuroimage, 147:976-984, 2017 Feb. PMID28041979.
3)
Klinkmueller
P, Kronenbuerger M,
Miao X, Bang J, Ultz KE, Paez A, Zhang X, Duan W, Margolis RL, Zijl PCV,
Ross CA, Hua J*. Impaired response of cerebral oxygen metabolism to
visual stimulation in Huntington's disease. J Cereb Blood Flow Metab. 2020
Aug 17;:271678X20949286. doi: 10.1177/0271678X20949286. [Epub ahead of
print] PubMed PMID: 32807001.
4.
Dynamic
imaging of small lymphatic vessels in the brain
The
circulation of cerebrospinal fluid (CSF) influences various aspects of
brain physiology, including substance distribution and waste clearance from
the brain parenchyma. Recently, cerebral vessels with typical endothelial markers
as lymphatic vessels in other organs in the body have been identified in
the dura mater alongside the dural venous sinuses, in regions around the
middle meningeal artery and cribriform plate, and in the basal part of the
skull in animal models. Some of the meningeal lymphatic vessels have also
been visualized in human brains. Cerebral lymphatic vessels are believed to
play an important role in the drainage of CSF into the cervical lymph
nodes, which has intriguing clinical implications for the clearance of
abnormal protein and other products in many brain diseases, such as
Alzheimer's disease and Parkinson's disease.
The
CSF space can be visualized on structural MR images with proper contrast
adjusted to the much longer longitudinal (T1) and transverse (T2)
relaxation times of CSF compared to the other tissues in the brain. When
gadolinium(Gd)-based contrast medium are used, MR signal contrast between
pre-contrast and post-contrast MR images can often be observed in the CSF
at certain locations within the intra-cranial space. This is mainly due to
the fact that the dural blood vessels lack a blood-brain barrier (BBB) that
presents in cortical blood vessels, which enables some of the commonly used
Gd contrast agents in human clinical MRI scans to cross the dural blood
vessel wall and to enter the CSF. Recent studies have shown that some
meningeal lymphatic vessels in the brain can be visualized using MRI with
Gd contrast in human brains.
However,
most existing approaches for the detection of Gd-based MR signal changes in
the CSF and cerebral lymphatic vessels typically take at least a few
minutes to achieve whole brain coverage and sufficient spatial resolution,
which provides a relatively low temporal resolution. Moreover, few studies
have performed a systemic investigation to optimize the contrast for the
detection of Gd-based signal changes in the CSF (most Gd studies focus on
Gd contrast in the blood). If the dynamic signal changes in the CSF and cerebral
lymphatic vessels before and after Gd administration can be tracked with
sufficient spatial and temporal resolution, it may serve as a useful tool
for the investigation of CSF drainage routes in the brain, which has not
been fully understood yet.
We
recently developed an MRI sequence to image Gd-based signal changes in the
CSF with a high temporal resolution (TR < 10 s), a fine spatial
resolution (1-0.65 mm isotropic voxel) and whole brain coverage on 3T and
7T human MRI scanners. With this method, dynamic signal changes and Gd
concentration can be quantified in the CSF space around several regions
containing cerebral lymphatics vessels in the brain, such as the dural
sinuses (superior sagittal sinus), middle meningeal artery, cribriform
plate (olfactory region) and basal brain regions (jugular foramen).
Figure from Cao
et al., Magn Reson Med. 2020 Jul 3;. doi: 10.1002/mrm.28389.
Selected publications:
1)
Cao D, Kang N, Pillai JJ, Miao X, Paez A,
Xu X, Xu J, Li X, Qin Q, Van Zijl PCM, Barker P, Hua J*. Fast whole brain MR imaging of dynamic susceptibility contrast
changes in the cerebrospinal fluid (cDSC MRI). Magn Reson Med. 2020 Jul 3;. doi:
10.1002/mrm.28389. [Epub ahead of print] PubMed PMID: 32621291.
5.
Ultra-high
magnetic field (7T) MRI and laminar fMRI
Ultra-high
magnetic field (7T and above) is expect to significantly boost the
intrinsic sensitivity of MRI, but also poses significant technical
challenges. Since the arrival of the 7T human MRI scanner at Johns Hopkins
in 2009, we have been working extensively on the development of functional
and physiological MRI techniques on 7T. In addition to routine high
resolution structural MRI scans such as MP2RAGE and FLAIR, we devised,
improved and optimized several advanced MRI pulse sequences for 7T
applications, including VASO, CEST and BOLD MRI. These methods have now
been used in a number of studies on 7T MRI scanners at Johns Hopkins, as
well as several other institutes in the US and abroad.
Figure: Delivery
of our 7T magnet at the F.M. Kirby Research Center for Functional Brian
Imaging on Sunday Nov 23 2009.
Laminar fMRI at 7T
The
enhanced sensitivity at 7T enables the performance of whole brain human
fMRI at a sub-millimeter (sub-mm) spatial resolution. In the human brain,
the thickness of functionally distinct layers is usually sub-mm. In
hierarchically organized brain systems, input and output signals arrive in
different layers of a given functional unit. The distance between such
input and output layers is in the range of 1-2mm in most brain regions.
Therefore, sub-mm fMRI allows the detection of neuronal activities at the
mesoscopic spatial regime of cortical layers, namely laminar (or layer-dependent
or cortical-depth-dependent) fMRI. Such layer specific information
can be used to infer directionality in brain circuits, whereas conventional
fMRI methods performed at the macroscopic scale can only provide
correlational information.
The
ability to resolve layer specific activities in brain circuits is of utmost
importance for neuroscience studies in healthy brains, as well as clinical
studies attempting to understand the mechanisms of brain diseases. For
instance, the memory circuit is well-known to be affected in many brain
diseases, such as dementia. Several models have been propose to understand
the information flow between different sub-regions in the medial temporal
lobe (MTL), a structure that plays a central role in the memory circuit.
Laminar fMRI offers the potential to probe the directionality of the
information flow through the detection of neuronal activities in different
layers of the entorhinal cortex (ERC, a key sub-region in the MTL)
predominantly responsible for encoding and retrieval. To distinguish these
segregated functions in the memory circuit is essential for studying the
mechanisms and for understanding potential disease specific changes in the
memory system. Using T2prep BOLD fMRI performed at sub-mm spatial
resolution at 7T during a memory task, differential laminar activities were
detected in the superficial and deep layers of the ERC associated with
information encoding and retrieval in healthy human brains.
Figure: Anatomical
location of the medial and lateral ERC. Coronal views of T1-weighted (1mm
iso-tropic voxel, whole brain), T2-weighted (0.5mm isotropic voxel, partial
brain) and T2prep BOLD fMRI images (0.9mm isotropic voxel, partial brain)
are shown. R: right, L: left; S: superficial layer, D: deep layer; M:
medial, L: lateral. The regions close to the CSF and WM are the superficial
and deep layers, respectively.
Figure:
Average laminar activation (beta) profile in the lateral and medial ERC
(n=9). The y-axis is the beta value for the contrast between successful
encoding and retrieval trials. The x-axis is the layer numbers. Layers
close to CSF and WM are superficial and deep layers, respectively. The beta
values in the shaded layers were averaged to give mean beta values in the
superficial (green) and deep (orange) layers, respectively. The error bars
indicate the inter-subject standard errors.
Selected publications:
1)
Hua J, Jones CK, Qin Q, Van Zijl PCM.
Implementation of Vascular-space-occupancy (VASO) MRI at 7 Tesla. Magnetic
Resonance in Medicine 69(4):1003-13, 2013. PMC4121129.
2)
Hua J, Qin Q, Van Zijl PCM, Pekar JJ, Jones
CK. Whole-brain three-dimensional T2-weighted BOLD functional magnetic
resonance imaging at 7 Tesla. Magnetic Resonance in Medicine 2014
Dec;72(6):1530-40. PMC4055555.
3)
Cheng
Y, Van Zijl
PCM, Hua J*. Measurement
of Parenchymal Extravascular R2* and Tissue Oxygen Extraction Fraction
Using Multi-echo VASO MRI at 7 Tesla. NMR in Biomedicine 2015
Feb;28(2):264-71. PMC4297270.
4)
Wu Y, Agarwal S, Jones CK, Webb AG, Van
Zijl PCM, Hua J*, Pillai J. Measurement of Arteriolar Blood Volume
in Brain Tumors Using MRI Without Exogenous Contrast Agent Administration
at 7T. Journal of Magnetic Resonance Imaging 2016 Nov;44(5):1244-1255.
PMC5045323.
5)
Hua J, Brandt AS, Lee S, Blair NIS, Wu Y,
Su L, Patel J, Faria AV, Lim IAL, Unschuld PG, Pekar JJ, Van Zijl PCM,
Ross CA, Margolis RL. Abnormal Grey Matter Arteriolar Cerebral Blood Volume
in Schizophrenia Measured With 3D Inflow-Based Vascular-Space-Occupancy MRI
at 7T. Schizophrenia Bulletin, 2017 May 1;43(3):620-632.
doi:10.1093/schbul/sbw109. PMC5464028.
6) Hua J, Blair NIS, Paez A, Choe A, Barber
AD, Brandt A, Lim IAL, Xu F, Kamath V, Pekar JJ, van Zijl PCM, Ross CA,
Margolis RL. Altered functional connectivity between sub-regions in the
thalamus and cortex in schizophrenia patients measured by resting state
BOLD fMRI at 7T. Schizophr Res. 2019 Apr;206:370-377. doi:
10.1016/j.schres.2018.10.016. Epub 2018 Nov 6. PubMed PMID: 30409697;
PubMed Central PMCID: PMC6500777
Applications
in brain diseases: selected publications
Huntington’s
disease (HD)
1)
Unschuld PG,
Liu X, Shanahan M, Margolis RL, Bassett SS, Brandt J, Schretlen DJ,
Redgrave GW, Hua J, Hock C, Reading SA, Van Zijl PCM, Pekar JJ, Ross
CA. Altered prefrontal network connectivity during a motor planning task in
prodromal Huntington's disease. Cortex 49(10):2661-73, 2013.
PMID23906595.
2)
Hua J, Unschuld PG, Margolis RL, Van Zijl
PCM, Ross CA. Elevated Arteriolar Cerebral Blood Volume in Prodromal
Huntington’s Disease Patients. Movement Disorders 29(3):396-401 2014.
PMC3834086.
3)
Van Bergen
JMG, Hua J, Unschuld PG, Lim IAL, Jones CK, Margolis RL, Ross CA,
Van Zijl PCM, Li X. Quantitative susceptibility mapping suggests altered
brain iron in premanifest Huntington’s disease. American Journal of
Neuroradiology 2016 May;37(5):789-96. PMC4867278.
4)
Chen L, Hua
J, Ross CA, Cai S, van Zijl PCM, Li X. Altered brain iron content and
deposition rate in Huntington's disease as indicated by quantitative
susceptibility MRI. J Neurosci Res. 2019 Apr;97(4):467-479. doi:
10.1002/jnr.24358. Epub 2018 Nov 29. PMID: 30489648. PMC6367012.
5)
Kronenbuerger
M, Hua J*, Bang JYA, Ultz KE, Miao X, Zhang X, Pekar JJ, Van Zijl
PCM, Duan W, Margolis RL, Ross CA. Differential Changes in Functional
Connectivity of Striatum-Prefrontal and Striatum-Motor Circuits in
Premanifest Huntington's Disease. Neurodegener Dis. 2019 Aug 14:1-10.
doi: 10.1159/000501616. PMID: 31412344.
6)
Klinkmueller
P, Kronenbuerger M,
Miao X, Bang J, Ultz KE, Paez A, Zhang X, Duan W, Margolis RL, Zijl PCV,
Ross CA, Hua J*. Impaired response of cerebral oxygen metabolism to
visual stimulation in Huntington's disease. J Cereb Blood Flow Metab. 2020
Aug 17;:271678X20949286. doi: 10.1177/0271678X20949286. [Epub ahead of
print] PubMed PMID: 32807001.
7)
Liu H, Chuangchuang Zhang, Jiadi Xu, Jing
Jin, Liam Cheng, Xinyuan Miao, Qian Wu, Zhiliang Wei, Peiying Liu, Hanzhang
Lu, Peter C. M. van Zijl, Christopher A. Ross, Hua J*, Wenzhen Duan*.
Huntingtin silencing delays onset and slows progression of Huntington’s
disease: a biomarker study. Brain. 2021 May 27;awab190. DOI:
10.1093/brain/awab190. PMID: 34043007.
Alzheimer’s
disease (AD)
1)
van Bergen
JM, Li X, Hua J, Schreiner SJ, Steininger SC, Quevenco FC, Wyss M,
Gietl AF, Treyer V, Leh SE, Buck F, Nitsch RM, Pruessmann KP, van Zijl PC,
Hock C, Unschuld PG. Colocalization of cerebral iron with Amyloid beta in
Mild Cognitive Impairment. Sci Rep. 2016 Oct 17;6:35514. PMC5066274.
2)
Quevenco FC,
Preti MG, van Bergen JM, Hua J, Wyss M, Li X, Schreiner SJ,
Steininger SC, Meyer R, Meier IB, Brickman AM, Leh SE, Gietl AF, Buck A,
Nitsch RM, Pruessmann KP, van Zijl PC, Hock C, Van De Ville D, Unschuld PG.
Memory performance-related dynamic brain connectivity indicates
pathological burden and genetic risk for Alzheimer's disease. Alzheimers
Res Ther. 2017 Mar 31;9(1):24. PMC5374623.
3)
Hua J, Lee S, Blair NIS, Wyss M, van
Bergen JMG, Schreiner SJ, Kagerer SM, Leh SE, Gietl AF, Treyer V, Buck A,
Nitsch RM, Pruessmann KP, Lu H, Van Zijl PCM, Albert M, Hock C, Unschuld
PG. Increased cerebral blood volume in small arterial vessels is a
correlate of amyloid-β-related cognitive decline. Neurobiol Aging
76:181-193, 2019 Jan. PMID: 30738323. PMC6438210.
Schizophrenia
1)
Hua J, Brandt AS, Lee S, Blair NIS, Wu Y,
Su L, Patel J, Faria AV, Lim IAL, Unschuld PG, Pekar JJ, Van Zijl PCM,
Ross CA, Margolis RL. Abnormal Grey Matter Arteriolar Cerebral Blood Volume
in Schizophrenia Measured With 3D Inflow-Based Vascular-Space-Occupancy MRI
at 7T. Schizophrenia Bulletin, 2017 May 1;43(3):620-632.
doi:10.1093/schbul/sbw109. PMC5464028.
2)
Brandt AS,
Unschuld PG, Lim IAL, Churchill G, Harris A, Pradhan S, Hua J,
Barker P, Ross CA, Van Zijl PCM, Edden R, Margolis RL. Age-related changes
in anterior cingulate cortex glutamate in schizophrenia: A 1H MRS Study at
7 Tesla. Schizophrenia Research 2016 Apr;172(1-3):101-5. PMC4821673.
3) Hua J, Blair NIS, Paez A, Choe A, Barber
AD, Brandt A, Lim IAL, Xu F, Kamath V, Pekar JJ, van Zijl PCM, Ross CA,
Margolis RL. Altered functional connectivity between sub-regions in the
thalamus and cortex in schizophrenia patients measured by resting state
BOLD fMRI at 7T. Schizophr Res. 2019 Apr;206:370-377. doi:
10.1016/j.schres.2018.10.016. Epub 2018 Nov 6. PubMed PMID: 30409697;
PubMed Central PMCID: PMC6500777
Presurgical
brain mapping in brain tumor and epilepsy
1)
Zaca D, Hua
J, Pillai JJ. Cerebrovascular reactivity mapping for brain tumor
presurgical planning. World J Clin Oncol. 2:289-98, 2011.
PMC3139032.
2)
Wu Y, Agarwal S, Jones CK, Webb AG, Van
Zijl PCM, Hua J*, Pillai J. Measurement of Arteriolar Blood Volume
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