The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are key factors in the pathophysiology of hypertension. Renal hypoxia is the putative mechanism stimulating both ...systems. Blood oxygen level-dependent MRI (BOLD-MRI) provides a noninvasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the relation between blood pressure (BP) and kidney function with renal BOLD-MRI. Moreover, the relation between direct and indirect variables of the RAAS and sympathetic nervous system and renal BOLD-MRI was studied.
Seventy-five hypertensive patients (38 men) were included. Antihypertensive medication was temporarily stopped. Patients collected urine during 24 h (sodium, catecholamines), blood samples were taken (creatinine, renin, aldosterone), a captopril challenge test was performed, and ambulatory BP was measured.
Mean age was 58 (±11) years, day-time BP was 167 (±19)/102 (±16) mmHg, and estimated glomerular filtration rate was 75 (±18) ml/min per 1.73 m). In multivariable regression analysis, renal medullary R2*-values inversely related to estimated glomerular filtration rate (P = 0.02). Moreover, the BP-lowering effect of captopril positively related to cortical (P = 0.02) and medullary (P = 0.008) R2*-values, as well as to P90 (P = 0.02).
In patients with hypertension, kidney function relates to medullary R2*-values. Activation of the RAAS is also positively related to the renal R2*-values.
Objectives
Renal multiparametric MRI (mpMRI) is a promising tool to monitor renal allograft health to enable timely treatment of chronic allograft nephropathy. This study aims to validate mpMRI by ...whole-kidney histology following transplantectomy.
Materials and methods
A patient with kidney transplant failure underwent mpMRI prior to transplantectomy. The mpMRI included blood oxygenation level-dependent (BOLD) MRI,
T
1
and
T
2
mapping, diffusion-weighted imaging (DWI), 2D phase contrast (2DPC) and arterial spin labeling (ASL). Parenchymal mpMRI measures were compared to normative values obtained in 19 healthy controls. Differences were expressed in standard deviations (SD) of normative values. The mpMRI measures were compared qualitatively to histology.
Results
The mpMRI showed a heterogeneous parenchyma consistent with extensive interstitial hemorrhage on histology. A global increase in
T
1
(+ 3.0 SD) and restricted diffusivity (− 3.6 SD) were consistent with inflammation and fibrosis. Decreased T
2
(− 1.8 SD) indicated fibrosis or hemorrhage. ASL showed diminished cortical perfusion (− 2.9 SD) with patent proximal arteries. 2DPC revealed a 69% decrease in renal perfusion. Histological evaluation showed a dense inflammatory infiltrate and fibrotic changes, consistent with mpMRI results. Most interlobular arteries were obliterated while proximal arteries were patent, consistent with ASL findings.
Discussion
mpMRI findings correlated well with histology both globally as well as locally.
Chemical exchange saturation transfer (CEST) exploits the chemical exchange of labile protons of an endogenous or exogenous compound with water to image the former indirectly through the water ...signal. Z-spectra of the brain have traditionally been analyzed for two most common saturation phenomena: downfield amide proton transfer (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body of brain metabolites, many of interest in neurology and oncology, contributes to the downfield saturation in Z-spectra. The extraction of these "hidden" metabolites from Z-spectra requires careful design of CEST sequences and data processing models, which is only possible by first obtaining CEST signatures of the brain metabolites possessing labile protons. In this work, we measured exchange rates of all major-for-CEST brain metabolites in the physiological pH range at 37 °C. Analysis of their contributions to Z-spectra revealed that regardless of the main magnetic field strength and pH, five main contributors, i.e. myo-inositol, creatine, phosphocreatine, glutamate, and mobile (poly)peptides, account for ca. 90% of downfield CEST effect. The fundamental CEST parameters presented in this study can be exploited in the design of novel CEST sequences and Z-spectra processing models, which will enable simultaneous and quantitative CEST imaging of multiple metabolites: multicolor CEST.
Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising ...applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p < 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p < 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.
High resolution BOLD fMRI has the potential to map activation patterns of small neuronal populations at the scale of cortical columns. However, BOLD fMRI does not measure neuronal activity, but only ...a correlate thereof, since it measures blood dynamics. To confirm that BOLD activation maps reflect neuronal population activity patterns, a direct comparison with neuro-electrophysiological data from the same cortical patch is necessary. Here, we compare BOLD activation patterns obtained with fMRI at 7T to electrophysiological patterns obtained with implanted high density electrocorticography (ECoG) grids in the same patch of human sensorimotor cortex, and with similar resolution (1.5mm). We used high spatially sampled high-frequency broadband (HFB) power from ECoG, which reflects local neuronal population activity. The spatial distribution of 7T BOLD activation matched the spatial distribution of ECoG HFB-power changes in the covered patch of sensorimotor cortex. BOLD fMRI activation foci were located within 1–3mm of the HFB-power ECoG foci. Both methods distinguished individual finger movement activation within a 1cm cortical patch, revealing a topographical medial to lateral layout for the little finger to index to thumb. These findings demonstrate that the BOLD signal at 7T is strongly correlated with the underlying electrophysiology, and is capable of discriminating patterns of neuronal population activity at a millimeter scale. The results further indicate the utility of 7T fMRI for investigation of intra-area organization of function and network dynamics.
•7T BOLD fMRI and intracranial ECoG at same high resolution from the same individuals•Same finger-topography for BOLD and ECoG in a 1cm patch of primary motor cortex•BOLD activation foci were located within 1–3mm of the ECoG activation foci•BOLD activation strongly matched to neuronal processes at the millimeter scale
The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic 1H-13C MRS during administration ...of 13C-labeled glucose. Proton-observed carbon-edited (POCE) MRS enhances the signal-to-noise ratio (SNR) compared with direct 13C-MRS. Ultra-high field further boosts the SNR and increases spectral dispersion; however, even at 7 T, Glu and Gln 1H-resonances may overlap. Further gain can be obtained with selective POCE (selPOCE). Our aim was to create a setup for indirect dynamic 1H-13C MRS in the human brain at 7 T. A home-built non-shielded transmit-receive 13C-birdcage head coil with eight transmit-receive 1H-dipole antennas was used together with a 32-channel 1H-receive array. Electromagnetic simulations were carried out to ensure that acquisitions remained within local and global head SAR limits. POCE-MRS was performed using slice-selective excitation with semi-localization by adiabatic selective refocusing (sLASER) and stimulated echo acquisition mode (STEAM) localization, and selPOCE-MRS using STEAM. Sequences were tested in a phantom containing non-enriched Glu and Gln, and in three healthy volunteers during uniformly labeled 13C-glucose infusions. In one subject the voxel position was alternated between bi-frontal and bi-occipital placement within one session. 4-13CGlu-H4 and 4-13CGln-H4 signals could be separately detected using both STEAM-POCE and STEAM-selPOCE in the phantom. In vivo, 4,5-13CGlx could be detected using both sLASER-POCE and STEAM-POCE, with similar sensitivities, but 4,5-13CGlu and 4,5-13CGln signals could not be completely resolved. STEAM-POCE was alternately performed bi-frontal and bi-occipital within a single session without repositioning of the subject, yielding similar results. With STEAM-selPOCE, 4,5-13CGlu and 4,5-13CGln could be clearly separated. We have shown that with our setup indirect dynamic 1H-13C MRS at 7 T is feasible in different locations in the brain within one session, and by using STEAM-selPOCE it is possible to separate Glu from Gln in vivo while obtaining high quality spectra.
Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to measure human brain function and relies on the assumption that hemodynamic changes mirror the ...underlying neuronal activity. However, an often reported saturation of the BOLD response at high movement rates has led to the notion of a mismatch in neurovascular coupling. We combined BOLD fMRI at 7T and intracranial electrocorticography (ECoG) to assess the relationship between BOLD and neuronal population activity in human sensorimotor cortex using a motor task with increasing movement rates. Though linear models failed to predict BOLD responses from the task, the measured BOLD and ECoG responses from the same tissue were in good agreement. Electrocorticography explained almost 80% of the mismatch between measured- and model-predicted BOLD responses, indicating that in human sensorimotor cortex, a large portion of the BOLD nonlinearity with respect to behavior (movement rate) is well predicted by electrophysiology. The results further suggest that other reported examples of BOLD mismatch may be related to neuronal processes, rather than to neurovascular uncoupling.
High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, ...confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (≈ 1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III-IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.
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