Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (⁠R1⁠), effective transverse relaxation rate (⁠R2∗⁠), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (⁠R2∗ at 3T, R1 at 7T), endothelial cells (⁠R1 and MTsat at 3T), microglia (⁠R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes and oligodendrocyte precursor cells (⁠R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types

Combining navigator and optical prospective motion correction for high-quality 500 μm resolution quantitative multi-parameter mapping at 7T

PURPOSE: High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients. METHODS: Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics. RESULTS: NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs. 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections. CONCLUSION: Navigator correction and PMC significantly improved the quality of PD, R1, and R2* maps, particularly in less compliant elderly volunteers and dementia patients

Interakce liposomů s porfyriny studována pomocí Ramanovy spektroskopie kapkově nanášených povlaků

Water-soluble cationic porphyrins have been studied in relation to antisense therapy and they have been successfully used to enhance the delivery of oligonu- cleotides to cells. The main focus of this study was to characterize the mech- anism of interaction of liposomes as model membranes, and porphyrins. We applied the drop coating deposition Raman spectroscopy (DCDR) to study com- plexes of liposomes and porphyrins. DCDR allowed us to measure complexes of low concentration as it uses the 'coffee ring' effect to concentrate the sample at the edge of a drop. We studied four different complexes combined of lipids: 1, 2−dipalmitoyl−sn−glycero−3−phosphocholine, 1, 2−dioleoyl−sn−glycero− 3 − phospho − (1 − rac − glycerol) and metalloporphyrins: copper 5, 10, 15, 20 − tetrakis(1 − methyl − 4 − pyridyl)porphyrin, copper 5, 10, 15, 20 − tetrakis(4 − sulfonatophenyl)porphyrin. We have found that the way these two components interact strongly depends on a specific lipid and porphyrin used. We observed partial incorporation of porphyrins into the liposome bilayer, their localisation to the surface of the liposome or the change of the conformation and ordering of lipid molecules. Moreover, we have found that the distribution of porphyrins in the dried drop is randomly non-homogenous. 6

Effects of temperature in the estimation of inhomogeneous magnetic transfer (ihMT) in post-mortem human brain

Inhomogeneous magnetic transfer (ihMT) is more sensitive to myelin macromolecules than standard MT proxies. Measuring ihMT in the multi-parameter mapping protocol allows calculating ihMT from MT saturation (MTsat) maps and thus inherently correct for the undesired dependencies on flip angle and the longitudinal relaxation rate. Further validation of this new ihMT metric requires measurement of MPM-based ihMT of human post-mortem material. Here, we showed that ihMT of a whole human post-mortem brain is feasible but can lead totemperature increase in the specimen, which is particularly pronounced in white matter

Measuring inhomogeneous MT (ihMT) in human brain by multi-parameter mapping (MPM)

Inhomogenous Magnetization Transfer (ihMT), the differential response to irradiation at single and dual frequency offsets, is sensitive to myelination. Quantification of ihMT in terms of MT saturation (MTsat), the percent reduction of Mz, corrects for underlying T1 and B1+ and allows comparing different implementations to optimize multi-parameter mapping (MPM) protocols. ihMTsat in white matter is roughly one twentieth of MTsat, merely 0.2 p.u. at 5kHz and 100% SAR at 3T. Noise propagation demands acquisition at 1.5mm resolution, large-array coils, and smaller offsets than suggested previously. Inverse MT ratios are highly correlated to ihMTs but obscure the true effect size

Understanding inhomogeneous MT (ihMT) in multi-parameter mapping of human brain: Towards larger ihMT, higher resolution, and influence of T1d

Inhomogenous Magnetization Transfer (ihMT), the differential response to irradiation at single and dual frequency offsets, is more complex than MT approaches. Expressing ihMT in terms of MT-saturation (ihMTsat) is a first step to quantification as it corrects for underlying T and B . Larger ihMTsat was observed for smaller frequency offsets, which is explained using MTsat as proxy for bound pool saturation. For longer TR, ihMTsat increased faster than MTsat indicating recovery of dipolar order as ihMTsat increased super-linearly to 1.1pu in WM and 0.2pu in GM at TR=52ms. ihMTsat mapping in vivo was performed at 1.3mm isotropic resolution

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (equation ImEquation1), effective transverse relaxation rate (equation ImEquation2), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (equation ImEquation3 at 3T, equation ImEquation4 at 7T), endothelial cells (equation ImEquation5 and MTsat at 3T), microglia (equation ImEquation6 and MTsat at 3T, equation ImEquation7 at 7T), and oligodendrocytes and oligodendrocyte precursor cells (equation ImEquation8 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis

Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (R1), effective transverse relaxation rate (R2∗), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (R2∗ at 3T, R1 at 7T), endothelial cells (R1 and MTsat at 3T), microglia (R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes (R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types