Xiufeng Li

Functional Imaging and Related Techniques: An Introduction for Rehabilitation Researchers

Over the past 25 years, techniques to image brain structure and function have offered investigators in the cognitive neurosciences and related fields unprecedented opportunities to study how human brain systems work and are connected. Indeed, the number of peer-reviewed research articles using these techniques has grown at an exponential rate during this period. Inevitably, investigators have become interested in mapping neuroplastic changes that support learning and memory using functional neuroimaging, and concomitantly, rehabilitation researchers have become interested in mapping changes in brain systems responsible for treatment effects during the rehabilitation of patients with stroke, traumatic brain injury, and other brain injury or disease. This new rehabilitation research and development arena is important because a greater understanding of how and why brain systems remap in the service of rehabilitation will lead to the development of better treatments. At the same time that functional neuroimaging methods have been developed, new structural neuroimaging techniques also have been added to the tool box of rehabilitation researchers. For example, diffusion tensor imaging (DTI) and related magnetic resonance (MR) techniques offer the ability to assess human white matter pathways in vivo. Not only can these techniques be used to estimate the integrity of a given volume of white matter, but they also can be used to trace fiber tracts within the brain. This latter development is exciting because most of what we know (or at least thought we knew) about the connections of the human cortex has actually come from research on nonhuman primates, leaving questions especially about the phylogenetically newer portions of the cortex. In the rehabilitation arena, a better understanding of how the brain’s connections are damaged could help us to predict what treatments are best for different research subjects and, eventually, might be useful in selecting the best treatment strategies for individual patients. Because the newer functional and structural neuroimaging techniques have enormous implications for rehabilitation research and development, it is highly desirable that rehabilitation researchers be able to evaluate the usefulness of the techniques for rehabilitation research and that the consumers of rehabilitation research (i.e., clinicians and researchers) be able to evaluate research findings that have applied the techniques. The purpose of this article is to discuss functional and structural imaging techniques used in rehabilitation research. We will not cover routine clinical MR or x-ray computerized tomography (CT) images. Rather, we will concentrate on a variety of techniques used most frequently, though not necessarily exclusively, in research settings. The article will consist of two main sections: (1) Because of the extraordinary versatility or MR techniques, the large number of MR techniques will be discussed first. (2) Subsequently, other functional neuroimaging techniques will be discussed, including: Positron Emission Tomography (PET), Magnetoencephalography/Magnetic Source Imaging (MEG/MSI), Near Infrared Spectroscopy (NIRS), Transcranial Magnetic Stimulation (TMS), and Electroencephalography/Evoked Potentials (EEG/EPs). For each imaging modality, we will give a brief explanation of the modality, its uses/potential uses in rehabilitation research, its strengths and limitations, and an example of research in the area.

Hippocampal Dysfunction in Gulf War Veterans: Investigation with ASL Perfusion MR Imaging and Physostigmine Challenge

PURPOSE To determine, with arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging and physostigmine challenge, if abnormal hippocampal blood flow in ill Gulf War veterans persists 11 years after initial testing with single photon emission computed tomography and nearly 20 years after the 1991 Gulf War. MATERIALS AND METHODS The local institutional review board approved this HIPAA-compliant study. Veterans were screened for contraindications and gave written informed consent before the study. In a semiblinded retrospective protocol, veterans in three Gulf War illness groups-syndrome 1 (impaired cognition), syndrome 2 (confusion-ataxia), and syndrome 3 (central neuropathic pain)-and a control group received intravenous infusions of saline in an initial session and physostigmine in a second session, 48 hours later. Each infusion was followed by measurement of hippocampal regional cerebral blood flow (rCBF) with pulsed ASL. A mixed-effects linear model adjusted for age was used to test for differences in rCBF after the cholinergic challenge across the four groups. RESULTS Physostigmine significantly decreased hippocampal rCBF in control subjects (P < .0005) and veterans with syndrome 1 (P < .05) but significantly increased hippocampal rCBF in veterans with syndrome 2 (P < .005) and veterans with syndrome 3 (P < .002). The abnormal increase in rCBF was found to have progressed to the left hippocampus of the veterans with syndrome 2 and to both hippocampi of the veterans with syndrome 3. CONCLUSION Chronic hippocampal perfusion dysfunction persists or worsens in veterans with certain Gulf War syndromes. ASL MR imaging examination of hippocampal rCBF in a cholinergic challenge experiment may be useful as a diagnostic test for this condition.

Simultaneous multi-slice Turbo-FLASH imaging with CAIPIRINHA for whole brain distortion-free pseudo-continuous arterial spin labeling at 3 and 7T

Simultaneous multi-slice (SMS) or multiband (MB) imaging has recently been attempted for arterial spin labeled (ASL) perfusion MRI in conjunction with echo-planar imaging (EPI) readout. It was found that SMS-EPI can reduce the T1 relaxation effect of the label and improve image coverage and resolution with little penalty in signal-to-noise ratio (SNR). However, EPI still suffers from geometric distortion and signal dropout from field inhomogeneity effects especially at high and ultrahigh magnetic fields. Here we present a novel scheme for achieving high fidelity distortion-free quantitative perfusion imaging by combining pseudo-continuous ASL (pCASL) with SMS Turbo-FLASH (TFL) readout at both 3 and 7 T. Bloch equation simulation was performed to characterize and optimize the TFL-based pCASL perfusion signal. Two MB factors (3 and 5) were implemented in SMS-TFL pCASL and compared with standard 2D TFL and EPI pCASL sequences. The temporal SNR of SMS-TFL pCASL relative to that of standard TFL pCASL was 0.76 ± 0.10 and 0.74 ± 0.11 at 7 T and 0.70 ± 0.05 and 0.65 ± 0.05 at 3T for MB factor of 3 and 5, respectively. By implementing background suppression in conjunction with SMS-TFL at 3T, the relative temporal SNR improved to 0.84 ± 0.09 and 0.79 ± 0.10 for MB factor of 3 and 5, respectively. Compared to EPI pCASL, significantly increased temporal SNR (p<0.001) and improved visualization of orbitofrontal cortex were achieved using SMS-TFL pCASL. By combining SMS acceleration with TFL pCASL, we demonstrated the feasibility for whole brain distortion-free quantitative mapping of cerebral blood flow at high and ultrahigh magnetic fields.

Perfusion deficit to cholinergic challenge in veterans with Gulf War Illness

A highly plausible etiology for Gulf War Illness (GWI) is that the neural damage and cognitive deficits are associated with excessive exposure to cholinesterase-inhibiting cholinergic stimulants. Our previous SPECT study provided strong indication that cerebral blood flow (CBF) in veterans with GWI may be different from those of unaffected control veterans. The present study confirmed and extended previous findings that patients with GWI have abnormal response to an inhibitory cholinergic challenge, physostigmine infusion, when compared to age-gender-education matched control veterans. The MRI-based arterial spin labeling (ASL) and phase-contrast techniques have several key advantages over SPECT, including shorter experiment duration, complete non-invasiveness, and higher spatial and temporal resolutions, and therefore may provide a cost-effective biomarker for characterization of GWI.

Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology

Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34) of patients with peripheral-zone and whole-gland models, respectively, compared with ADC alone. Model-based CBS maps for cancer detection showed improved visualization of cancer location and extent. Conclusion Quantitative multiparametric MR imaging models developed by using coregistered correlative histopathologic data yielded a voxel-wise CBS that outperformed single quantitative MR imaging parameters for detection of prostate cancer, especially when the models were assessed at the individual level. (©) RSNA, 2016 Online supplemental material is available for this article.

Theoretical and experimental evaluation of multi-band EPI for high-resolution whole brain pCASL Imaging.

Multi-band echo planar imaging (MB-EPI), a new approach to increase data acquisition efficiency and/or temporal resolution, has the potential to overcome critical limitations of standard acquisition strategies for obtaining high-resolution whole brain perfusion imaging using arterial spin labeling (ASL). However, the use of MB also introduces confounding effects, such as spatially varying amplified thermal noise and leakage contamination, which have not been evaluated to date as to their effect on cerebral blood flow (CBF) estimation. In this study, both the potential benefits and confounding effects of MB-EPI were systematically evaluated through both simulation and experimentally using a pseudo-continuous arterial spin labeling (pCASL) strategy. These studies revealed that the amplified noise, given by the geometry factor (g-factor), and the leakage contamination, assessed by the total leakage factor (TLF), have a minimal impact on CBF estimation. Furthermore, it is demonstrated that MB-EPI greatly benefits high-resolution whole brain pCASL studies in terms of improved spatial and temporal signal-to-noise ratio efficiencies, and increases compliance with the assumptions of the commonly used single blood compartment model, resulting in improved CBF estimates.

Feasibility of measuring prostate perfusion with arterial spin labeling

Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility‐induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole‐body transmit coil and external receiver array, global prostate perfusion can be measured with arterial spin labeling at 3 T. In five healthy subjects with a mean age of 44 years, the mean total prostate blood flow was measured to be 25.8 ± 7.1 mL/100 cm3/min, with an estimated bolus duration and arterial transit time of 884 ± 209 ms and 721 ± 131 ms, respectively. Copyright

Anteroposterior perfusion heterogeneity in human hippocampus measured by arterial spin labeling MRI

Measurements of blood flow in the human hippocampus are complicated by its relatively small size, unusual anatomy and patterns of blood supply. Only a handful of arterial spin labeling (ASL) MRI articles have reported regional cerebral blood flow (rCBF) values for the human hippocampus. Numerous reports have found heterogeneity in a number of other physiological and biochemical parameters along the longitudinal hippocampal axis. There is, however, only one ASL study of perfusion properties as a function of anteroposterior location in the hippocampus, reporting that rCBF is lower and the arterial transit time (ATT) is longer in the anterior hippocampus than in the posterior hippocampus of the rat brain. The purpose of this article was to measure ATT and rCBF in anterior, middle and posterior normal adult human hippocampus. To better distinguish anteroposterior perfusion heterogeneity in the hippocampus, a modified ASL method, called Orthogonally Positioned Tagging Imaging Method for Arterial Labeling with Flow‐sensitive Alternating Inversion Recovery (OPTIMAL FAIR), was developed that provides high in‐plane resolution with oblique coronal imaging slices perpendicular to the long axis of the hippocampus to minimize partial volume effects. Perfusion studies performed with this modified FAIR method at 3 T indicated that anterior, middle and posterior human hippocampus segments have unique transit time and rCBF values. Of these three longitudinal hippocampal regions, the middle hippocampus has the highest perfusion and the shortest transit time and the anterior hippocampus has the lowest perfusion and the longest transit time. Copyright

7 T renal MRI:challenges and promises

The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging.

Measuring renal tissue relaxation times at 7 T

As developments in RF coils and RF management strategies make performing ultra‐high‐field renal imaging feasible, understanding the relaxation times of the tissue becomes increasingly important for tissue characterization, sequence optimization and quantitative functional renal imaging, such as renal perfusion imaging using arterial spin labeling. By using a magnetization‐prepared single‐breath‐hold fast spin echo imaging method, human renal T1 and T2 imaging studies were successfully performed at 7 T with 11 healthy volunteers (eight males, 45 ± 17 years, and three females, 29 ± 7 years, mean ± standard deviation, S.D.) while addressing challenges of B1+ inhomogeneity and short‐term specific absorption rate limits. At 7 T, measured renal T1 values for the renal cortex and medulla (mean ± S.D.) from five healthy volunteers who participated in both 3 T and two‐session 7 T studies were 1661 ± 68 ms and 2094 ± 67 ms, and T2 values were 108 ± 7 ms and 126 ± 6 ms. For comparison, similar measurements were made at 3 T, where renal cortex and medulla T1 values of 1261 ± 86 ms and 1676 ± 94 ms and T2 values of 121 ± 5 ms and 138 ± 7 ms were obtained. Measurements at 3 T and 7 T were significantly different for both T1 and T2 values in both renal tissues. Reproducibility studies at 7 T demonstrated that T1 and T2 estimations were robust, with group mean percentage differences of less than 4%. Copyright