Cristina Rossi

Histogram analysis of renal arterial spin labeling perfusion data reveals differences between volunteers and patients with mild chronic kidney disease.

ObjectiveThe spatial heterogeneity of renal perfusion data was analyzed with arterial spin labeling (ASL) data sets in a cohort of subjects with moderately impaired kidney function (ie, glomerular filtration rate >30 mL/min/1.73 m2) versus a cohort of healthy volunteers. The potential diagnostic value of a detailed histogram analysis of such perfusion data for detection of mild renal dysfunction was investigated. Materials and MethodsEight healthy volunteers and 9 patients with mild renal dysfunction (chronic kidney disease stages 1-3) were included in the study. All subjects underwent ASL perfusion measurements with a 1.5-T magnetic resonance scanner using a flow-sensitive alternating inversion recovery labeling scheme with true fast imaging in steady-state precession data readout. Quantitative perfusion maps were generated using extended Bloch equations. Histogram analysis was performed to quantify the metrics of the perfusion of the renal cortex and the entire parenchyma, respectively. Mean perfusion value (&mgr;), SD of the mean value (&sgr;), peak height (PH), peak position (PP), skewness (s), and kurtosis (k) were computed to describe the distribution of the perfusion values. ResultsA significant difference was found in the mean perfusion values computed for the cortex and the parenchyma between healthy volunteers (cortex, 329 ± 53 mL/100 g/min; parenchyma, 301 ± 51 mL/100 g/min) and patients (cortex, 263 ± 81 mL/100 g/min; parenchyma, 244 ± 77 mL/100 g/min). The histogram analysis of the cortical perfusion values also showed a significant difference (P < 0.05) in the main histogram measures between healthy volunteers (PP = 368 ± 65 mL/100 g/min; s = −0.543 ± 0.298; k = 0.371 ± 0.590) and patients (PP = 237 ± 115 mL/100 g/min; s = −0.125 ± 0.581; k = −0.151 ± 0.561). ConclusionModerate renal dysfunction is associated with a significant change in the distribution of cortical perfusion values and a reduction of blood perfusion for both the parenchyma and the cortex. The preliminary results reported in this study suggest the importance of a regional assessment of renal perfusion. Histogram analysis of ASL data may help to detect chronic kidney disorders and to monitor their progression in a clinical setting.

Non-parametric intravoxel incoherent motion analysis in patients with intracranial lesions: Test-retest reliability and correlation with arterial spin labeling

Intravoxel incoherent motion (IVIM) analysis of diffusion imaging data provides biomarkers of true passive water diffusion and perfusion properties. A new IVIM algorithm with variable adjustment of the b-value threshold separating diffusion and perfusion effects was applied for cerebral tissue characterization in healthy volunteers, computation of test-retest reliability, correlation with arterial spin labeling, and assessment of applicability in a small cohort of patients with malignant intracranial masses. The main results of this study are threefold: (i) accounting for regional differences in the separation of the perfusion and the diffusion components improves the reliability of the model parameters; (ii) if differences in the b-value threshold are not accounted for, a significant tissue-dependent systematic bias of the IVIM parameters occurs; (iii) accounting for voxel-wise differences in the b-value threshold improves the correlation with CBF measurements in healthy volunteers and patients. The proposed algorithm provides a robust characterization of regional micro-vascularization and cellularity without a priori assumptions on tissue diffusion properties. The glioblastoma multiforme with its inherently high variability of tumor vascularization and tumor cell density may benefit from a non-invasive clinical characterization of diffusion and perfusion properties.

The IVIM signal in the healthy cerebral gray matter: A play of spherical and non-spherical components

ABSTRACT The intra‐voxel incoherent motion (IVIM) model assumes that blood flowing in isotropically distributed capillary segments induces a phase dispersion of the MR signal, which increases the signal attenuation in diffusion‐weighted images. However, in most tissue types the capillary network has an anisotropic micro‐architecture. In this study, we investigated the possibility to indirectly infer the anisotropy of the capillary network in the healthy cerebral gray matter by evaluating the dependence of the IVIM signal from the direction of the diffusion‐encoding. Perfusion‐related indices and self‐diffusion were modelled as symmetric rank 2 tensors. The geometry of the tensors was quantified pixel‐wise by decomposing the tensor in sphere‐like, plane‐like, and line‐like components. Additionally, trace and fractional anisotropy of the tensors were computed. While the self‐diffusion tensor is dominated by a spherical geometry with a residual contribution of the non‐spherical components, both, fraction of perfusion and pseudo‐diffusion, present a substantial (in the order of 30%) contribution of planar and linear components to the tensor metrics. This study shows that the IVIM perfusion estimates in the cerebral gray matter present a detectable deviation from the spherical model. These non‐spherical components may reflect the direction‐dependent morphology of the microcirculation. Therefore, the tensor generalization of the IVIM model may provide a tool for the non‐invasive monitoring of cerebral capillary micro‐architecture during development, aging or in pathologies. Graphical abstract Figure. No Caption available. HighlightsTensor analysis reveals anisotropy of the IVIM signal in cerebral gray matter.Planar and linear components contribute to approx. 30% of the metric of the tensors.Fraction of perfusion anisotropy may reflect the morphometry of the microcirculation.The anisotropy of the pseudo‐diffusion may provide functional information.IVIM tensor imaging allows for quantitative characterization of microcirculation.

Probing neuronal activation by functional quantitative susceptibility mapping under a visual paradigm: A group level comparison with BOLD fMRI and PET

Dynamic changes of brain-tissue magnetic susceptibility provide the basis for functional MR imaging (fMRI) via T2*-weighted signal-intensity modulations. Promising initial work on a detection of neuronal activity via quantitative susceptibility mapping (fQSM) has been published but consistently reported on ill-understood positive and negative activation patterns (Balla et al., 2014; Chen and Calhoun, 2015a). We set out to (i) demonstrate that fQSM can exploit established fMRI data acquisition and processing methods and to (ii) better describe aspects of the apparent activation patterns using fMRI and PET as standards of reference. Under a standardized visual-stimulation paradigm PET and 3-T gradient-echo EPI-based fQSM, fMRI data from 9 healthy volunteers were acquired and analyzed by means of Independent Component Analysis (ICA) at subject level and, for the first time, at group level. Numbers of activated (z-score>2.0) voxels were counted and their mean z-scores calculated in volumes of interest (occipital lobe (Nocc_lobe), segmented occipital gray-matter (NGM_occ_lobe), large veins (Nveins)), and in occipital-lobe voxels commonly activated in fQSM and fMRI component maps. Common but not entirely congruent regions of apparent activation were found in the occipital lobe in z-score maps from all modalities, fQSM, fMRI and PET, with distinct BOLD-negatively correlated regions in fQSM data. At subject-level, Nocc_lobe, NGM_occ_lobe and their mean z-scores were significantly smaller in fQSM than in fMRI, but their ratio, NGM_occ_lobe/Nocc_lobe, was comparable. Nveins did not statistically differ and the ratio Nveins/NGM_occ_lobe as well as the mean z-scores were higher for fQSM than for fMRI. In veins and immediate vicinity, z-score maps derived from both phase and fQSM-data showed positive and negative lobes resembling dipole shapes in simulated field and phase maps with no correlate in fMRI or PET data. Our results show that standard fMRI tools can directly be used for fQSM processing, and suggest that fQSM may have the potential to detect gray-matter activation distant from large veins, to improve detection of veins with stimulus-induced venous oxygen saturation (SvO2) variations, and to better localize areas of activation. However, our results seem to clearly expose issues that phenomenologically resemble an incomplete dipolar inversion and that need to be subject to further investigation.

Effect of respiratory hyperoxic challenge on magnetic susceptibility in human brain assessed by quantitative susceptibility mapping (QSM).

The purpose of this study was to measure the regional change of magnetic susceptibility in human brain upon inhalation of 100% oxygen by MRI quantitative susceptibility mapping (QSM). Fourteen healthy volunteers were scanned in a 3 T MR scanner with a 3D multi‐gradient‐echo sequence while breathing medical air (normoxia) and pure oxygen (hyperoxia). QSM images and R2* maps were calculated. Mean susceptibility differences versus white matter were measured in regions of interest covering veins, gray matter (GM), and cerebrospinal fluid (CSF) under both conditions. Hyperoxia resulted in a strong susceptibility decrease in large veins (−154.4 ± 65.9 ppb, p < 10−6), in a smaller reduction in GM (−1.3 ± 1 ppb, p < 0.001), and in a susceptibility increase in ventricular CSF (3.8 ± 1.8 ppb, p < 10−5). The susceptibility decrease in veins implied an increase of venous oxygen saturation (SvO2) by 10.1 ± 4.0%. Compared with QSM, R2* was more seriously affected by long‐distance effects not related to local tissue oxygenation and increased in cerebral frontal regions (3 ± 2 s−1, p < 0.0004) due to paramagnetic molecular oxygen in cavities. The results highlight the potential of QSM to yield region‐specific quantitative oxygenation information, and, thus, for applications such as oxygen‐therapy monitoring or identification of hypoxic tumor tissue during radiotherapy planning. Copyright

Clinical Functional MRI of the kidneys

In functional renal magnetic resonance imaging (MRI), advanced techniques are applied to obtain information on a functional and molecular level from the kidney tissue beyond pure morphology. Techniques such as diffusion-weighted and diffusion tensor imaging, arterial spin labelling, and blood oxygenation level-dependent imaging provide potential biomarkers of organ function. Moreover, dynamic contrast-enhanced techniques after the intra-venous injection of gadolinium-chelates may be used to assess glomerular filtration and urinary excretion. This review summarizes recent developments of contrast- and non-contrast-enhanced MRI techniques for assessment of renal function in a clinical setting. The physiological background and the sequence techniques are described in detail. Potential clinical applications of the different techniques are discussed regarding their potential usefulness in the assessment of parenchymal diseases, urinary tract anomalies, transplant kidney function, and renal masses.

Renal Arterial Spin Labeling Magnetic Resonance Imaging.

Arterial spin labeling (ASL) MRI allows the quantification of tissue perfusion without administration of exogenous contrast agents. Patients with reduced renal function or other contraindications to Gadolinium-based contrast media may benefit from the non-invasive monitoring of tissue microcirculation. So far, only few studies have investigated the sensitivity, the specificity and the reliability of the ASL techniques for the assessment of renal perfusion. Moreover, only little is known about the interplay between ASL markers of perfusion and functional renal filtration parameters. In this editorial, we discuss the main technical issues related to the quantification of renal perfusion by ASL and, in particular, the latest results in patients with kidney disorders.

Investigation of the pulsatility of cerebrospinal fluid using cardiac-gated Intravoxel Incoherent Motion imaging

ABSTRACT The quantitative and non‐invasive monitoring of cerebrospinal fluid (CSF) dynamics and composition may have high clinical relevance in the management of CSF disorders. In this study, we propose the use of the Intravoxel Incoherent Motion (IVIM) MRI for obtaining simultaneous measurements of CSF self‐diffusion and fluid circulation. The rationale for this study was that turbulent fluid and mesoscopic fluid fluctuations can be modeled in a first approximation as a fast diffusion process. In this case, we expect that the fast fluid circulation and slower molecular diffusion dynamics can be quantified, assuming a bi‐exponential attenuation pattern of the diffusion‐weighted signal in MRI. IVIM indexes of fast and slow diffusion measured at different sites of the CSF system were systematically evaluated depending on both the phase of the heart cycle and the direction of the diffusion‐encoding. The IVIM measurements were compared to dynamic measurements of fluid circulation performed by phase‐contrast MRI. Concerning the dependence on the diffusion/flow‐encoding direction, similar patterns were found both in the fraction of fast diffusion, f, and in the fluid velocity. Generally, we observed a moderate to high correlation between the fraction of fast diffusion and the maximum fluid velocity along the high‐flow directions. Exploratory data analysis detected similarities in the dependency of the fraction of fast diffusion and of the velocity from the phase of the cardiac cycle. However, no significant differences were found between parameters measured during different phases of the cardiac cycle. Our results suggest that the fraction of fast diffusion may reflect CSF circulation. The bi‐exponential IVIM model potentially allows us to disentangle the two diffusion components of the CSF dynamics by providing measurements of fluid cellularity (via the slow‐diffusion coefficient) and circulation (via the fraction of fast‐diffusion index). Graphical abstract Figure. No Caption available. HighlightsThe fraction of fast diffusion in the IVIM model reflects CSF circulation.Cardiac‐gated IVIM measures fluid diffusion and circulation.IVIM complements phase‐contrast MRI in the assessment of CSF dynamics.

Reduction of BOLD interference in pseudo-continuous arterial spin labeling: towards quantitative fMRI

Fluctuations in blood-oxygenation level dependent (BOLD) signal and perfusion affect the quantification of changes in cerebral blood flow (CBF), coupled to neuronal activity, in arterial spin labeling (ASL). Subtraction methods for control and labeled MR images (i.e. pair-wise, surround subtraction, and subtraction of sinc-interpolated images), postulated to mitigate this interference in pseudo-continuous ASL (pCASL), were evaluated by comparison with quantitative 15O-water PET. At rest, a good agreement in the CBF values was found between PET and MRI for each of the subtraction methods. Stimulation of the visual system resulted in a regional CBF increase in the occipital lobe, which was detectable in both modalities. Bland–Altman analysis showed a systematic underestimation of the CBF values during activation in MRI. Evaluation of the relative CBF change induced by neuronal stimulation showed good inter-modality agreement for the three subtraction methods. Perfusion data obtained with each subtraction method followed the stimulation paradigm without significant differences in the correlation patterns or in the time lag between stimulation and perfusion response. Comparison to the gold standard confirmed the detectability of a neuronal stimulation pattern by pCASL. The results indicate that the combined use of background suppression and short TE reduces the BOLD-weighting in the pCASL signal.

Prediction of small for size syndrome after extended hepatectomy: Tissue characterization by relaxometry, diffusion weighted magnetic resonance imaging and magnetization transfer

This study aimed to monitor the course of liver regeneration by multiparametric magnetic-resonance imaging (MRI) after partial liver resection characterizing Small-for-Size Syndrome (SFSS), which frequently leads to fatal post-hepatectomy liver failure (PLF). Twenty-two C57BL/6 mice underwent either conventional 70% partial hepatectomy (cPH), extended 86% partial hepatectomy (ePH) or SHAM operation. Subsequent MRI scans on days 0, 1, 2, 3, 5 and 7 in a 4.7T MR Scanner quantified longitudinal and transverse relaxation times, apparent diffusion coefficient (ADC) and the magnetization-transfer ratio (MTR) of the regenerating liver parenchyma. Histological examination was performed by hematoxylin-eosin staining. After hepatectomy, an increase of T1 time was detected being larger for ePH on day 1: 18% for cPH vs. 40% for ePH and on day 2: 24% for cPH vs. 49% for ePH. An increase in T2 time, again greater in ePH was most pronounced on day 5: 21% for cPH vs. 41% for ePH. ADC and MTR showed a decrease on day 1: 21% for ePH vs. 13% for cPH for ADC, 15% for ePH vs. 11% for cPH for MTR. Subsequently, all MR parameters converged towards initial values in surviving animals. Dying PLF animals exhibited the strongest increase of T1 relaxation time and most prominent decreases of ADC and MTR. The retrieved MRI biomarkers indicate SFSS and potentially developing PLF at an early stage, likely reflecting cellular hypertrophy with extended water content and concomitantly diluted cellular components as features of liver regeneration, appearing more intense in ePH as compared to cPH.