Chan-Hong Moon

Multiscale Pattern Analysis of Orientation-Selective Activity in the Primary Visual Cortex

Although orientation columns are less than a millimeter in width, recent neuroimaging studies indicate that viewed orientations can be decoded from cortical activity patterns sampled at relatively coarse resolutions of several millimeters. One proposal is that these differential signals arise from random spatial irregularities in the columnar map. However, direct support for this hypothesis has yet to be obtained. Here, we used high-field, high-resolution functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to determine the spatial scales at which orientation-selective information can be found in the primary visual cortex (V1) of cats and humans. We applied a multiscale pattern analysis approach in which fine- and coarse-scale signals were first removed by ideal spatial lowpass and highpass filters, and the residual activity patterns then analyzed by linear classifiers. Cat visual cortex, imaged at 0.3125 mm resolution, showed a strong orientation signal at the scale of individual columns. Nonetheless, reliable orientation bias could still be found at spatial scales of several millimeters. In the human visual cortex, imaged at 1 mm resolution, a majority of orientation information was found on scales of millimeters, with small contributions from global spatial biases exceeding ∼1 cm. Our high-resolution imaging results demonstrate a reliable millimeters-scale orientation signal, likely emerging from irregular spatial arrangements of orientation columns and their supporting vasculature. fMRI pattern analysis methods are thus likely to be sensitive to signals originating from other irregular columnar structures elsewhere in the brain.

Mapping Iso-Orientation Columns by Contrast Agent-Enhanced Functional Magnetic Resonance Imaging: Reproducibility, Specificity, and Evaluation by Optical Imaging of Intrinsic Signal

Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.

Neural Interpretation of Blood Oxygenation Level-Dependent fMRI Maps at Submillimeter Columnar Resolution

Whether conventional gradient-echo (GE) blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is able to map submillimeter-scale functional columns remains debatable mainly because of the spatially nonspecific large vessel contribution, poor sensitivity and reproducibility, and lack of independent evaluation. Furthermore, if the results from optical imaging of intrinsic signals are directly applicable, regions with the highest BOLD signals may indicate neurally inactive domains rather than active columns when multiple columns are activated. To examine these issues, we performed BOLD fMRI at a magnetic field of 9.4 tesla to map orientation-selective columns of isoflurane-anesthetized cats. We could not convincingly map orientation columns using conventional block-design stimulation and differential analysis method because of large fluctuations of signals. However, we successfully obtained GE BOLD iso-orientation maps with high reproducibility (r = 0.74) using temporally encoded continuous cyclic orientation stimulation with Fourier data analysis, which reduces orientation-nonselective signals such as draining artifacts and is less sensitive to signal fluctuations. We further reduced large vessel contribution using the improved spin-echo (SE) BOLD method but with overall decreased sensitivity. Both GE and SE BOLD iso-orientation maps excluding large pial vascular regions were significantly correlated to maps with a known neural interpretation, which were obtained in contrast agent-aided cerebral blood volume fMRI and total hemoglobin-based optical imaging of intrinsic signals at a hemoglobin iso-sbestic point (570 nm). These results suggest that, unlike the expectation from deoxyhemoglobin-based optical imaging studies, the highest BOLD signals are localized to the sites of increased neural activity when column-nonselective signals are suppressed.

Compatible dual-echo arteriovenography (CODEA) using an echo-specific K-space reordering scheme.

An improved dual‐echo sequence magentic resonance (MR) imaging technique was developed to simultaneously acquire a time‐of‐flight MR angiogram (MRA) and a blood oxygenation level‐dependent MR venogram (MRV) in a single MR acquisition at 3 T. MRA and MRV require conflicting scan conditions (e.g., excitation RF profile, flip angle, and spatial presaturation pulse) for their optimal image quality. This conflict was not well counterbalanced or reconciled in previous methods reported for simultaneous acquisition of MRA and MRV. In our dual‐echo sequence method, an echo‐specific K‐space reordering scheme was used to uncouple the scan parameter requirements for MRA and MRV. The MRA and MRV vascular contrast was enhanced by maximally separating the K‐space center regions acquired for the MRA and MRV, and by adjusting and applying scan parameters compatible between the MRA and MRV. As a preliminary result, we were able to acquire a simultaneous dual‐echo MRA and MRV with image quality comparable to that of the conventional single‐echo MRA and MRV that were acquired separately at two different sessions. Furthermore, integrated with tilted optimized nonsaturating excitation and multiple overlapping thin‐slab acquisition techniques, our dual‐echo MRA and MRV provided seamless vascular continuity over a large coverage volume of the brain anatomy. Magn Reson Med, 2009.

Dual‐echo arteriovenography imaging with 7T MRI

To implement a dual‐echo sequence MRI technique at 7T for simultaneous acquisition of time‐of‐flight (TOF) MR angiogram (MRA) and blood oxygenation level‐dependent (BOLD) MR venogram (MRV) in a single MR acquisition and to compare the image qualities with those acquired at 3T.

Dual-Echo Arteriovenography Imaging with 7 Tesla MR

To implement a dual‐echo sequence MRI technique at 7T for simultaneous acquisition of time‐of‐flight (TOF) MR angiogram (MRA) and blood oxygenation level‐dependent (BOLD) MR venogram (MRV) in a single MR acquisition and to compare the image qualities with those acquired at 3T.

Application of compatible dual-echo arteriovenography in stroke: Preliminary observations

Compatible dual‐echo arteriovenography (CODEA) is a recent MRI technique for simultaneous acquisition of an MR angiogram (MRA) and MR venogram (MRV) with image quality comparable to conventional single‐echo acquisitions. The purpose of this study was to evaluate the utility of CODEA in imaging patients with chronic stroke and to test the utility of a new image representation technique (“enhanced maximum intensity projection [MIP]) based on tissue segmentation, intensity inversion, and vessel enhancement filtering) for MRV. Arterial and venous abnormalities associated with stroke were delineated on MRA and MRV acquired simultaneously with the CODEA technique. CODEA MRV displayed with the enhanced MIP technique facilitated the visualization of the overall venous structures in 3D. Reduced venous vascularity was detected in the regions of arterial occlusion compared to the contralateral normal brain regions. The CODEA technique along with the enhanced MIP technique may be valuable, particularly in clinical applications that require efficient MRA/MRV imaging because of limited scan time such as in acute stroke.

Quantitative evaluation of k-space reordering schemes for compatible dual-echo arteriovenography (CODEA).

Compatible dual‐echo arteriovenography (CODEA) is a recently developed technique for simultaneous acquisition of time‐of‐flight MR angiogram (MRA) and blood oxygenation level–dependent MR venogram (MRV) using an echo‐specific k‐space reordering scheme. In this study, we evaluated and compared the image quality of CODEA MRA/MRV implemented with two different schemes of echo‐specific k‐space reordering: one along the 1st phase‐encode direction (one‐dimensional) only and the other along both phase‐encode directions (two‐dimensional). Our results showed that use of the two‐dimensional reordering scheme improved contrast‐to‐noise ratio of small arteries by ∼8%, although not statistically significant (P > 0.1). Contrast‐to‐noise ratio of the CODEA MRAs was better than that for the non‐CODEA dual‐echo MRA without k‐space reordering (contrast‐to‐noise ratio increased in large arteries by ∼10% and small arteries by ∼45%; P < 0.1). Contrast‐to‐noise ratio of the CODEA MRAs was comparable with that of the conventional single‐echo MRA for large arteries but reduced by ∼20% for small arteries. Contrast‐to‐noise ratio of veins on the CODEA MRVs was equivalent to that of the conventional single‐echo and the non‐CODEA dual‐echo MRVs. However, some veins in the CODEA MRVs showed stronger contrast than those in the single‐echo MRV in relation to the contrast of neighboring arterial signals. Magn Reson Med 63:1404–1410, 2010.

Is MRI Detection of Kidney Iron Deposition Increased in Haptoglobin 2-2 Genotype Carriers with Type 1 Diabetes?

Haptoglobins (Hp) main role is to bind free hemoglobin (Hb), reducing its oxidative potential. The Hp-Hb complex formed is cleared from the circulation by macrophage receptor CD163. In diabetes, impaired Hp 2-2-Hb CD163 clearance and abnormal glomerular permeability allow the large Hp 2-2-Hb complex to cross the barrier, where its redox active iron leads to cellular toxicity. Although Hp 2-2 predicts renal function decline, whether renal iron deposition differs by Hp is unknown. We used renal quantitative T2* magnetic resonance imaging to estimate iron level in the cortex and medullar of type 1 diabetes (T1D) adults [15 Hp 1-1 and 15 Hp 2-2 carriers of similar age (53 years), duration (45 years), and gender]. Total kidney iron level was estimated as the sum of the cortex and medullar iron. Albuminuria was defined as urinary albumin to creatinine ratio >30 mg/g in two of three samples. Total kidney iron did not differ by gender or Hp but was higher in those with albuminuria (p = 0.05), an association confined to Hp 2-2 carriers (p = 0.04 vs. p = 0.51 in Hp 1-1). These data lead to the hypothesis that kidney iron deposition is increased among Hp 2-2 carriers with albuminuria in T1D. Antioxid. Redox Signal. 29, 735-741.

Dual-echo arteriovenography imaging with 7T MRI: CODEA with 7T

To implement a dual‐echo sequence MRI technique at 7T for simultaneous acquisition of time‐of‐flight (TOF) MR angiogram (MRA) and blood oxygenation level‐dependent (BOLD) MR venogram (MRV) in a single MR acquisition and to compare the image qualities with those acquired at 3T.