Edmund Kwok

In vivo intermolecular double-quantum imaging on a clinical 1.5 T MR scanner

A novel MRI method based on the intermolecular double‐quantum coherence (DQC) for soft tissues is described. DQC images of human brain were obtained for the first time on a whole‐body 1.5 T scanner. The combination of quantum and classical formalisms was used to characterize multiple‐quantum coherences, and to aid in the design of a DQC imaging sequence. The theoretical analysis suggests that signals from the intermolecular DQCs have higher sensitivity than those from the zero‐quantum coherence (ZQC) for human brain, and the sensitivity increases with increased field strength. The DQC signal may provide a new form of contrast for MRI. Magn Reson Med 43:335–341, 2000.

A multi-center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysis

To demonstrate the technical feasibility and reliability of a multi‐center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N‐acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC).

fMRI of auditory stimulation with intermolecular double‐quantum coherences (iDQCs) at 1.5T

An intermolecular double‐quantum coherence (iDQC) imaging technique was used to study auditory activation in the human brain at 1.5T with a dual temporal lobe surface phased array coil and a quadrature head coil. Preliminary results demonstrate that it is feasible to obtain auditory activation maps using iDQC imaging at 1.5T, both in individual subjects using the surface coil array and with multisubject averaging of data using the head coil. The most robust activation map was obtained when a spin‐echo (SE) acquisition was combined with an iDQC excitation. Since SE with conventional single quantum coherence (SQC) and similar parameters showed much reduced activation in spite of its higher signal‐to‐noise ratio (SNR), it was determined that activation resulting from the SE‐iDQC acquisition almost entirely originates from iDQCs. In addition, the fact that the robust activation was obtained using signals at an evolution time more sensitive to changes in magnetic susceptibilities also suggests the sensitivity of iDQCs to the BOLD effect upon activation. iDQCs provide a novel MRI method which is potentially more sensitive to the BOLD effect traditionally measured with SQC. Magn Reson Med 45:356–364, 2001.

MRI and Quantification of Draining Lymph Node Function in Inflammatory Arthritis

Abstract:  While erosion and tissue necrosis are the end‐stage result of inflammatory arthritis, factors that can predict their initiation and severity are unknown. In an effort to identify these prognostic factors we developed contrast‐enhanced (CE)‐magnetic resonance imaging (MRI) for the mouse knee to assess the pathogenesis of inflammatory arthritis. Using this approach to study synovitis and draining lymph node (LN) function we first demonstrated that the LNs of TNF‐Tg mice at 5 months are significantly larger and have greater enhancement in comparison to wild‐type (WT) mice. This difference correlated with the abundance of dilated LYVE‐1+ sinuses in the draining LNs. Dynamic CE‐MRI further demonstrated differences between TNF‐Tg and WT mice in the kinetics of LN enhancement. We established an LN capacity (LNcap) measurement that is a function of both volume and CE. We demonstrated that TNF‐Tg mice have a 15‐fold increase over WT levels at 5 months age (P < 0.001). Amelioration of arthritis with anti‐TNF therapy resulted in a significant decrease in LNcap (P < 0.0001) that approached WT levels within 4 weeks. Interestingly, this functional decrease was not associated with a reduction of lymphatic vessels, which persist after therapy in both LNs and synovium. To assess the relationship between draining LN function and synovitis, a regression analysis was performed that demonstrated a significant negative correlation (R2= 0.63, P= 0.01) between LNcap and synovial volume. TNF‐Tg mice with a lower LNcap display an accelerated progression of arthritis. These results indicate a protective function of enhanced lymphatic drainage in inflammatory arthritis.

Enhanced sensitivity to molecular diffusion with intermolecular double-quantum coherences: implications and potential applications

Apparent molecular self-diffusion rates for (1)H intermolecular double-quantum coherences (iDQCs) were measured in solvents covering a wide range of intrinsic diffusion coefficients at 1.5, 9.4 and 14T, and water iDQC diffusion-weighted images were obtained at 1.5T in human brains and at 9.4T in rat brains. Conventional single quantum coherence (SQC) measurements were also made in the same samples. Experimental results indicate that iDQCs are approximately twice as sensitive to diffusion as SQC. A general theoretical expression was derived, and a model was proposed to explain the phenomenon. Potential applications in DWI and brain fMRI were also discussed.

New image contrast mechanisms in intermolecular double-quantum coherence human MR imaging.

We have developed a novel magnetic resonance imaging (MRI) method based on the intermolecular double‐quantum coherence (DQC) in humans. Combined quantum mechanical and classical formalisms were used to characterize the signal and to aid in the design of a DQC imaging sequence with conventional or echoplanar acquisitions. Imaging contrast was evaluated in volunteers using a 1.5‐T clinical scanner. The results demonstrated that the DQC images have contrasts fundamentally different from the conventional images based on single‐quantum coherence (SQC). Both our theoretical analysis and experiments suggest that signals from DQCs have a higher signal‐to‐noise ratio than those from zero‐quantum coherence (ZQC) for human brain imaging. The new contrast in DQC imaging may be useful for the detection of varying microstructures, potentially improving the detection of tumors without the need for contrast agents and providing a higher sensitivity and selectivity to magnetic susceptibility distributions in functional MRI brain studies. J. Magn. Reson. Imaging 2000;12:311–320.

Predicting regional variations in trabecular bone mechanical properties within the human proximal tibia using MR imaging

Trabecular bone density changes throughout the proximal tibia are indicative of several musculoskeletal disorders of the knee joint. Many of these disorders involve not only changes in the amount of bone, but also in the surrounding soft tissue. Osteoarthritis, for instance, involves bone density changes below the subchondral bone and throughout the proximal tibia, along with degradation evident in the articular cartilage. Osteoporosis, characterized by low bone density may also involve changes in bone size, structure or microarchitecture, each of which may contribute to fracture risk. Recent studies have shown that magnetic resonance (MR) imaging, most frequently applied for soft tissue imaging, also allows non-invasive 3-dimensional characterization of bone microstructure. The purpose of the current study is to use whole joint MR images to acquire regional apparent bone volume fraction (appBVF) throughout the proximal tibia and correlate with mechanical properties measured on the corresponding ex vivo specimens. To compare our method to a high-resolution imaging modality, micro-CT analysis was performed in a subset of specimens. Using linear mixed-effects models, significant correlations (p<0.05) were determined between MR appBVF and Youngs modulus (r(2)=0.58, MPSE=3633 MPa(2)), yield stress (r(2)=0.73, MPSE=1.53 MPa(2)) and ultimate stress (r(2)=0.72, MPSE=2.29 MPa(2)). Comparable significant correlations (p<0.05) were also determined between micro-CT BVF and Youngs modulus (r(2)=0.47, MPSE=5179 MPa(2)), yield stress (r(2)=0.80, MPSE=1.23 MPa(2)) and ultimate stress (r(2)=0.83, MPSE=1.76 MPa(2)). The current study demonstrates that MR imaging may be used as an in vivo imaging tool to determine differences in bone strength between subjects and regional variations within a single tibia.

T1 measurements in cell cultures: A new tool for characterizing contrast agents at 1.5T

The objective of this work was to assess the feasibility and accuracy of T1 and relaxivity measurements in cell cultures using 1.5T magnetic resonance imaging (MRI) with the long‐term goal to develop a tool for evaluation of novel paramagnetic agents in a realistic macromolecular environment. This initial study was carried out using MCF‐7 cells treated with independently determined concentrations of Gd‐DTPA. Two cell culture systems were evaluated: cell pellets and single layers of cells grown on microporous inserts. High‐resolution T1 measurements of cell cultures were acquired with two dimensional Inversion Recovery Fast Spin Echo (2D‐IR‐FSE), three dimensional Inversion Recovery Fast Spin Echo (3D‐IR‐FSE), and 3D‐SPGR sequences. The T1 and relaxivity accuracy of these sequences was confirmed with aqueous Gd‐DTPA samples of known concentration. Relaxivities of 1.71 ± 0.15 [mM−1second−1] and 1.55 ± 0.50 [mM−1second−1] were measured in the cell pellets and cell monolayers, respectively, and were different from the value of 4.3 [mM−1second−1] for Gd‐DTPA in water. Both cell pellets and monolayers are suitable for initial assessment of novel MR contrast agents. J. Magn. Reson. Imaging 2001;14:636–648.

Functional MR imaging of vision in the deaf.

RATIONALE AND OBJECTIVES Early loss of a sensory modality has been associated with cortical reorganization in both animal models and humans. The purpose of this study was to map visual activation with functional magnetic resonance (MR) imaging and to document possible developmental reorganization in the temporal lobe caused by early deafness. MATERIALS AND METHODS Six prelingual, profoundly deaf subjects were compared with a similar group of six hearing subjects. Three visual tasks were performed by both groups: attention to movement in the field-of-view periphery, shape matching, and mental rotation. Echo-planar coronal MR imaging was performed at 1.5 T. RESULTS Regions of interest encompassing the middle and posterior aspects of the superior and middle temporal gyri demonstrated a significantly (P < .05) increased activation in deaf subjects compared with hearing subjects, particularly on the right side (P < .05) and during the tasks involving motion. The most specific effect was noted during the mental-rotation task. CONCLUSION These results support the hypothesis that portions of the temporal lobe usually involved in auditory processing are more active during certain visual tasks in deaf compared with hearing subjects. Cortical reorganization may be an important factor in the deaf population when considering the physiology of temporal lobe lesions and predicting surgical outcomes. Functional MR imaging may be helpful during preoperative assessment in individuals with deafness.

Chronic axial compression of the mouse tail segment induces MRI bone marrow edema changes that correlate with increased marrow vasculature and cellularity.

Magnetic resonance imaging (MRI) of bone marrow edema (BME) has been found to be helpful in the diagnosis of back pain attributed to degenerative disk disease (DDD) and spondyloarthropathy (SA), but its interpretation is limited by a lack of knowledge of its nature and natural history. We assessed effects of compressive forces to mouse tail segments of WT and TNF‐Tg mice with SA, via contrast enhanced‐MRI and histology. Normalized marrow contrast enhancement (NMCE) of uninstrumented WT vertebrae significantly decrease, threefold (p < 0.01) from 8 to 12 weeks of age, while the NMCE of TNF‐Tg vertebrae remained elevated. Compressive loading (6× body weight) increased NMCE twofold (p < 0.02) within 2 weeks in WT tails, which was equal to 6× loaded TNF‐Tg tails within 4 weeks. Histology confirmed degenerative changes and that load‐induced NMCE corresponded to increased vascular sinus tissue (35 ± 3% vs. 19 ± 3%; p < 0.01) and cellularity (4,235 ± 886 vs.1,468 ± 320 cells/mm2; p < 0.01) for the loaded versus unloaded WT, respectively. However, micro‐computed tomography (CT) analyses failed to detect significant load‐induced changes to bone. While the bone marrow of loaded WT and TNF‐Tg vertebrae were similar, histology demonstrated mild cellular infiltrate and increased osteoclastic resorption in the WT tails versus severe inflammatory‐erosive arthritis in TNF‐Tg joints. Significant (p < 0.05) decreases in cortical and trabecular bone volume in uninstrumented TNF‐Tg versus WT vertebrae were confirmed by micro‐CT. Thus, chronic load‐induced DDD causes BME signals in vertebrae similar to those observed from SA, and both DDD and SA signals correlate with a conversion from yellow to red marrow, with increased vascularity.