Blood Flow Maps Research Articles

Myocardial perfusion in cardiac amyloidosis.

Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Echo time-dependent observed T1 and quantitative perfusion in chronic obstructive pulmonary disease using magnetic resonance imaging.

Due to hypoxic vasoconstriction, perfusion is interesting in the lungs. Magnetic Resonance Imaging (MRI) perfusion imaging based on Dynamic Contrast Enhancement (DCE) has been demonstrated in patients with Chronic Obstructive Pulmonary Diseases (COPD) using visual scores, and quantification methods were recently developed further. Inter-patient correlations of echo time-dependent observed T1 [T1(TE)] have been shown with perfusion scores, pulmonary function testing, and quantitative computed tomography. Here, we examined T1(TE) quantification and quantitative perfusion MRI together and investigated both inter-patient and local correlations between T1(TE) and quantitative perfusion. 22 patients (age 68.0 ± 6.2) with COPD were examined using morphological MRI, inversion recovery multi-echo 2D ultra-short TE (UTE) in 1-2 slices for T1(TE) mapping, and 4D Time-resolved angiography With Stochastic Trajectories (TWIST) for DCE. T1(TE) maps were calculated from 2D UTE at five TEs from 70 to 2,300 μs. Pulmonary Blood Flow (PBF) and perfusion defect (QDP) maps were produced from DCE measurements. Lungs were automatically segmented on UTE images and morphological MRI and these segmentations registered to DCE images. DCE images were separately registered to UTE in corresponding slices and divided into corresponding subdivisions. Spearman's correlation coefficients were calculated for inter-patient correlations using the entire segmented slices and for local correlations separately using registered images and subdivisions for each TE. Median T1(TE) in normal and defect areas according to QDP maps were compared. Inter-patient correlations were strongest on average at TE2 = 500 μs, reaching up to |ρ| = 0.64 for T1 with PBF and |ρ| = 0.76 with QDP. Generally, local correlations of T1 with PBF were weaker at TE2 than at TE1 or TE3 and with maximum values of |ρ| = 0.66 (from registration) and |ρ| = 0.69 (from subdivision). In 18 patients, T1 was shorter in defect areas than in normal areas, with the relative difference smallest at TE2. The inter-patient correlations of T1 with PBF and QDP found show similar strength and TE-dependence as those previously reported for visual perfusion scores and quantitative computed tomography. The local correlations and median T1 suggest that not only base T1 but also the TE-dependence of observed T1 in normal areas is closer to that found previously in healthy volunteers than in defect areas.

Time-resolved Laser Speckle Contrast Imaging (TR-LSCI) of Cerebral Blood Flow.

To address many of the deficiencies in optical neuroimaging technologies, such as poor tempo-spatial resolution, low penetration depth, contact-based measurement, and time-consuming image reconstruction, a novel, noncontact, portable, time-resolved laser speckle contrast imaging (TR-LSCI) technique has been developed for continuous, fast, and high-resolution 2D mapping of cerebral blood flow (CBF) at different depths of the head. TR-LSCI illuminates the head with picosecond-pulsed, coherent, widefield near-infrared light and synchronizes a fast, high-resolution, gated single-photon avalanche diode camera to selectively collect diffuse photons with longer pathlengths through the head, thus improving the accuracy of CBF measurement in the deep brain. The reconstruction of a CBF map was dramatically expedited by incorporating convolution functions with parallel computations. The performance of TR-LSCI was evaluated using head-simulating phantoms with known properties and in-vivo rodents with varied hemodynamic challenges to the brain. TR-LSCI enabled mapping CBF variations at different depths with a sampling rate of up to 1 Hz and spatial resolutions ranging from tens/hundreds of micrometers on rodent head surfaces to 1-2 millimeters in deep brains. With additional improvements and validation in larger populations against established methods, we anticipate offering a noncontact, fast, high-resolution, portable, and affordable brain imager for fundamental neuroscience research in animals and for translational studies in humans.

Monoacylglycerol Lipase Inhibition Using ABX-1431 Attenuates Cerebral Ischaemia Early After Traumatic Brain Injury.

An early event in the pathology of traumatic brain injury (TBI) is a reduction in cerebral blood flow (CBF), which exacerbates secondary injury development and inhibits brain recovery. The endogenous cannabinoid system signalling (eCBs) might be critical in TBI recovery due to modulating synaptic activity and exerting neuroprotective and anti-inflammatory effects. In the brain, eCBs predominantly occur at cannabinoid receptor type 1 via the eCB 2-arachidonoylglycerol (2-AG). The aim of this work was to test the efficacy of potentiating 2-AG signalling by monoacylglycerol lipase (MAGL) inhibition using ABX-1431 immediately following TBI. Laser speckle contrast imaging (LSCI) was used to create a high-resolution map of regional cerebral blood flow (CBF) over the pericontusion cortical surface. In-vivo two-photon laser scanning microscopy (2PLSM) was used to monitor cerebral microcirculation (i.v. fluorescein isothiocyanate dextran, FITC) and mitochondrial respiration and brain tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence, NADH) during 4hours after CHI. After baseline imaging, male C57BL/6 J mice (10-12weeks, >28g) were subjected to a modified moderate Shohami weight-drop closed-head injury (CHI) followed by i.p. injection of ABX-1431 (5mg/kg) or vehicle 30 min after the insult (10 mice per group). Differences between groups and between time points were determined using two-way repeated measures (ANOVA) for multiple comparisons and post hoc testing with the statistical significance level set at p<0.05. Optical imaging revealed that CHI caused a decrease in regional CBF, arteriole diameters (vasospasm), and blood flow volume, leading to capillary microthrombosis and a reduction in capillary flow velocity. Compromised cerebral microcirculation led to the development of tissue hypoxia. ABX-1431 application, in a ~30-minute delay, mitigated the development of microvascular dysfunction, microthrombosis formation, and tissue hypoxia compared to the saline control group (p<0.05, starting 1hour after CHI). Therefore, MAGL inhibition by ABX-1431 attenuates cerebral ischaemia early after TBI. The observed 2-AG-mediated cerebrovascular relaxation might involve both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium.

Role of Histogram Features on Arterial Spin Labeling Perfusion Magnetic Resonance Imaging in Identifying Isocitrate Dehydrogenase Genotypes and Glioma Malignancies.

To explore the use of histogram features on noninvasive arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in differentiating isocitrate dehydrogenase mutant-type (IDH-mut) from isocitrate dehydrogenase wild-type (IDH-wt) gliomas, and lower-grade gliomas (LGGs) from glioblastomas. This retrospective study included 131 patients who underwent ASL MRI and anatomic MRI. Cerebral blood flow (CBF) maps were calculated, from which 10 histogram features describing the CBF distribution were extracted within the tumor region. Correlation analysis was performed to determine the correlations between histogram features as well as tumor grades and IDH genotypes. The independent t-test and Fisher's exact test were used to determine differences in the extracted histogram features, age at diagnosis, and sex in different glioma subtypes. Multivariate binary logistic regression analysis was performed, and diagnostic performances were evaluated with the receiver operating characteristic curves. CBF histogram features were significantly correlated with tumor grades and IDH genotypes. These features can effectively differentiate LGGs from glioblastomas, and IDH-mut from IDH-wt gliomas. The area under the receiving operating characteristic curve of the model calculated using combined CBF 30th percentile and age at diagnosis in differentiating LGGs from glioblastomas was 0.73. Integrating age at diagnosis and CBF 10th percentile could be more effective in differentiating IDH-mut from IDH-wt gliomas. Furthermore, the combined model had a better area under the receiving operating characteristic curve at 0.856 (sensitivity: 84.4%, specificity: 82.9%). The histogram features on ASL were significantly correlated with tumor grade and IDH genotypes. Moreover, the use of these features could effectively differentiate glioma subtypes. The combined application of age at diagnosis and perfusion histogram features resulted in a more comprehensive identification of tumor subtypes. Therefore, ASL can be a noninvasive tool for the pre-surgical evaluation of gliomas.

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aβ Knock‐In (hAβKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAβKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodsContrast‐enhanced PWI MRI (9.4T) was undertaken from hAβKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultsCompared to WT mice at 18mo of age, hAβKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAβKI only mice.ConclusionsThe 18mo hAβKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).

Cerebral perfusion is elevated in a novel model of aged hAβKI APOE4 mice

AbstractBackgroundThe Model Organism Development and Evaluation for Late‐Onset Alzheimer’s Disease (MODEL‐AD) Consortium is developing the next generation of Alzheimer’s disease (AD) models based on human genomic and imaging data. Recently, MODEL‐AD has generated a new human Aß Knock‐In (hAßKI) mouse carrying the APOE4 allele. APOE4 carriers are at increased risk for AD. Previous studies have demonstrated altered cerebrovascular integrity and function. We examined the cerebrovascular function in the hAßKI APOE4 mice at 18mo of age using perfusion‐weighted magnetic resonance imaging (PWI). We investigated brain‐wide perfusion alterations in conjunction with histopathological vessel painting.MethodContrast‐enhanced PWI MRI (9.4T) was undertaken from hAßKI APOE4 (n = 6) and WT (n = 5) mice at 18mo of age following tail vein cannulation for Gadolinium infusion. Imaging sequences included: T1‐pre and post‐infusion, PWI (10min) and susceptibility‐weighted imaging (SWI) for blood extravasation and iron content. All data were processed using JIM v9 software for maps of cerebral blood flow (CBF), volumes (CBV), time to peak, mean transit time and dynamic susceptibility measures for blood‐brain barrier dysfunction. Manual regions of interest (ROI) were performed for cortex, temporal lobe cortex, dorsal hippocampus and thalamus, and semi‐automatic 30+ regions based on the Allen mouse brain atlas. At the end of the in vivo experiments all mice underwent vessel painting followed by microscopic analyses.ResultCompared to WT mice at 18mo of age, hAßKI APOE4 mice exhibited elevated CBF in virtually all regions examined. CBF was elevated approx. 16%, 11%, 4% and 23% in the cortex, hippocampus, thalamus and temporal lobe cortex, respectively. CBF was significantly elevated in the retrosplenial and temporal lobe cortices (p&lt;0.05). CBV was also significantly increased in temporal lobe. Ongoing analyses will correlate vascular network measures (density, junctions, length) to PWI metrics as well as to hAßKI only mice.ConclusionThe 18mo hAßKI APOE4 mouse compared to WT exhibited consistent brain‐wide elevations in cerebrovascular measures. This increase may represent a compensatory mechanism to maintain decreased metabolism that occurs with aging. The MODEL‐AD consortium (UCI/IUSM/JAX) continues to develop new and novel AD mouse models. All data will be made available to AD researchers via the Sage Knowledge Network (https://adknowledgeportal.synapse.org/).

Changes in choroidal hemodynamics of form-deprivation myopia in Guinea pigs

PurposeWe studied changes in the choroid, particularly variation in blood flow, during the development of myopia. The hemodynamic mechanism in play remains unclear. We evaluated blood flow by quantitating indocyanine green (ICG) fluorescence in a guinea pig model of form-deprivation myopia. MethodsGuinea pigs were divided into form-deprivation myopia (FDM) and normal control (NC) groups. Ocular biometric and choroidal hemodynamics parameters were quantitatively derived via ICG imaging, and included the maximal ICG fluorescence intensity (Imax), rising time (Trising), blood flow index (BFI), and mean transit time (MTT). ResultsForm deprivation was associated with significant interocular differences in terms of both refractive error and axial length. ICG fluorescence hemodynamic maps of fundal blood flow and vasculature density were evident. In deprived eyes, the fluorescence signals exhibited significantly longer Trising and MTT but lower Imax and BFI than fellow eyes and NC group. The interocular differences in terms of the ocular biometric and hemodynamic parameters were significantly correlated. Hemodynamic analysis of choriocapillaris lobules revealed weakened fluorescence intensity and prolonged arrival and filling times in deprived eyes. Form deprivation reduced the number of lobulated choriocapillaris structures. ConclusionForm-deprivation myopia triggered changes in the hemodynamic and vascular network structures of the choroid and choriocapillaris. The ICG fluorescence imaging/analysis method provides a unique tool for further myopia research.

Depth-sensitive diffuse speckle contrast topography for high-density mapping of cerebral blood flow in rodents

Depth-sensitive diffuse speckle contrast topography for high-density mapping of cerebral blood flow in rodents

Integration of orthogonal Fourier profilometry with blood flow mapping for 3D fingertip biometric authentication

We present herein the combination of Fourier transform profilometry based orthogonal projection with a laser speckle imaging method to provide three-dimensional (3D) fingertip blood flow imaging and shape reconstruction for biometric authentication purposes. In the proposed approach, orthogonal sinusoidal grating patterns with a fixed spatial frequency emanating from a digital projector first illuminate the surface of a person's finger. Then, the projector is blocked and a laser source illuminates the finger. The projector and laser work alternately such that only one source illuminates the finger at a given time allowing no illumination crosstalk between the two devices. The deformed grating patterns and the diffuse backscattered laser light, respectively, are recorded on the same CCD camera. In the computer, the 3D shape of the finger is reconstructed simultaneously with a blood flow map of the finger. Finally, the images are merged yielding a dynamic flow topography visualization of the person's finger. This dual-modality strategy utilizes the strengths of each imaging method in a complementary way, thus enabling simple 3D shape recovery and characterization of a specific user, and increasing the specificity of authentication security. The method is experimentally validated on both human and fake fingers through VanderLugt optical correlation framework. Overall, the results demonstrate the utility of our proposed approach for biometric authentication. We envision that our optoelectronic setup could be potentially integrated into a wide variety security platform.

Decoupling of Regional Cerebral Blood Flow and Brain Function Along the Alzheimer's Disease Continuum.

Alzheimer's disease (AD) is accompanied with impaired neurovascular coupling. However, its early alteration remains elusive along the AD continuum. This study aimed to investigate the early disruption of neurovascular coupling in cognitively normal (CN) and mild cognitive impairment (MCI) elderly and its association with cognition and AD pathologies. We included 43 amyloid-β-negative CN participants and 38 amyloid-β-positive individuals (18 CN and 20 MCI) from the Alzheimer's Disease Neuroimaging Initiative dataset. Regional homogeneity (ReHo) map was used to represent neuronal activity and cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Neurovascular coupling was assessed by CBF/ReHo ratio at the voxel level. Analyses of covariance to detect the between-group differences and to further investigate the relations between CBF/ReHo ratio and AD biomarkers or cognition. In addition, the correlation of cerebral small vessel disease (SVD) burden and neurovascular coupling was assessed as well. Related to amyloid-β-negative CN group, amyloid-β-positive groups showed decreased CBF/ReHo ratio mainly in the left medial and inferior temporal gyrus. Furthermore, lower CBF/ReHo ratio was associated with a lower Mini-Mental State Examination score as well as higher AD pathological burden. No association between CBF/ReHo ratio and SVD burden was observed. AD pathology is a major correlate of the disturbed neurovascular coupling along the AD continuum, independent of SVD pathology. The CBF/ReHo ratio may be an index for detecting neurovascular coupling abnormalities, which could be used for early diagnosis in the future.

Measurements of slow tissue dynamics with short-separation speckle contrast optical spectroscopy.

Laser speckle contrast imaging (LSCI) measures 2D maps of cerebral blood flow (CBF) in small animal brains such as mice. The contrast measured in LSCI also includes the static and slow-varying components that contain information about brain tissue dynamics. But these components are less studied as compared to the fast dynamics of CBF. In traditional wide-field LSCI, the contrast measured in the tissue is largely contaminated by neighboring blood vessels, which reduces the sensitivity to these static and slow components. Our goal is to enhance the sensitivity of the contrast to static and slow tissue dynamics and test models to quantify the characteristics of these components. To achieve this, we have developed a short-separation speckle contrast optical spectroscopy (ss-SCOS) system by implementing point illumination and point detection using multi-mode fiber arrays to enhance the static and slow components in speckle contrast measurements as compared to traditional wide-field LSCI (WF-LSCI). We observed larger fractions of the static and slow components when measured in the tissue using ss-SCOS than in traditional LSCI for the same animal and region of interest. We have also established models to obtain the fractions of the static and slow components and quantify the decorrelation time constants of the intensity auto-correlation function for both fast blood flow and slower tissue dynamics. Using ss-SCOS, we demonstrate the variations of fast and slow brain dynamics in animals before and post-stroke, as well as within an hour post-euthanasia. This technique establishes the foundation to measure brain tissue dynamics other than CBF, such as intracellular motility.

Evaluation of single-delay arterial spin labeling-based spatial coefficient of variation and histogram-based parameters in relation to cerebrovascular reserve in patients with Moyamoya disease.

Single-delay Arterial Spin Labeling (ASL)-based spatial coefficient of variation (CoVCBF) has been suggested as a measure of hemodynamic disturbance in patients with cerebrovascular diseases. However, spatial CoVCBF and other histogram-based parameters such as skewness and kurtosis and the volume of the arterial transit time artefact (ATAvol), has not been evaluated in patients with MMD nor against cerebrovascular reserve (CVR). The aim of this study was to assess whether any associations between spatial CoVCBF, skewness, kurtosis, and ATAvol are present and to analyze any potential associations with CVR, derived from single-delay ASL in patients with MMD. Fifteen MMD patients were included before or after revascularization surgery. Cerebral blood flow (CBF) maps were acquired using pseudo-continuous ASL before, and 5, 15, and 25 min after an intravenous acetazolamide injection. CVRmax was defined as the highest percentual increase in CBF at any of the three post-injection time points. A vascular territory template was spatially normalized to each patient, including the bilateral anterior, middle, and posterior cerebral arteries. All affected anterior and middle cerebral artery regions and all unaffected posterior cerebral artery regions were included, based on Suzuki grading by digital subtraction angiography. Significant differences between affected and unaffected regions were found for CBF, CVRmax, and ATAvol. No association was found between CVRmax and any other parameter. High correlations were found between spatial CoVCBF, skewness and ATAvol. Spatial CoVCBF derived from single-delay ASL does not correlate with CVR in patients with MMD. Moreover, skewness and kurtosis did not provide additional information of clinical value.

Prostate perfusion mapping using Fourier-transform based velocity-selective arterial spin labeling: Choice of cutoff velocity and comparison with brain.

To develop velocity selective arterial spin labeling (VSASL) protocols for prostate blood flow (PBF) and prostate blood volume (PBV) mapping. Fourier-transform based velocity-selective inversion and saturation pulse trains were utilized in VSASL sequences to obtain blood flow and blood volume weighted perfusion signal, respectively. Here four cutoff velocities (Vcut = 0.25, 0.50, 1.00, and 1.50 cm/s) for PBF and PBV mapping sequences were evaluated with a parallel implementation in brain for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV) with identical 3D readout. This study was performed at 3T on eight young and middle-aged healthy subjects comparing both perfusion weighted signal (PWS) and temporal SNR (tSNR). In contrast to CBF and CBV, the PWS of PBF and PBV were rather unobservable at Vcut of 1.00 or 1.50 cm/s and both PWS and tSNR of PBF and PBV considerably increased at the lower Vcut , indicating that blood moves much slower in prostate than in brain. Similar to the brain results, the tSNR of PBV-weighted signal was about two to four times over the corresponding values of PBF-weighted signal. The results also suggested a trend of reduced vascularity within prostate during aging. For prostate, a low Vcut of 0.25-0.50 cm/s seemed necessary for both PBF and PBV measurements to obtain adequate perfusion signal. As in brain, PBV mapping yielded a higher tSNR than PBF.

Left Ventricular Outflow Obstruction in D-Transposition of Great Arteries: A Rare Etiology

A 2-day old neonate [gender: male; weight: 3.2 kg; height: 53cm] presented to the authors institution with an arterial oxygen saturation of 74%. The child was receiving 6 cm H2O continuous positive airway pressure therapy [FIO2: 0.5] and was treated with a prostaglandin E1 infusion [10ng/kg/min]. Transthoracic echocardiography revealed situs solitus, levocardia, normal systemic and pulmonary venous drainage and a 6 mm non-restrictive atrial septal defect with a left to right shunt. The atrioventricular connections were concordant. The aorta was arising from the right ventricle with no right ventricular outflow obstruction [Figure 1]. The pulmonary artery was arising from the left ventricle with confluent good size branch pulmonary arteries with posterior deviation of the conal septum [Figure 2]. A large perimembranous (conoventricular type)1 ventricular septal defect with an inlet [6 mm] and outlet [6 mm] extension and an additional tiny apical defect were demonstrated [Figure 3]. A patent ductus arteriosus [2.7 mm] shunting left to right was also present (not shown). A 2-dimensional echocardiography image in the parasternal long axis view displayed an obstruction to the left ventricular outflow tract [white arrow] and a color Doppler blood flow map demonstrated turbulence in the outflow tract [Figure 4A,B]. In the subcostal view with the probe tilted anteriorly, color flow Doppler mapping showed the ventricular septal defect and also the blood flow acceleration across the left ventricular outflow tract [Figure 5, videolip-1]. At the area of turbulence, the jet width was 0.234 cm[Figure 6A]. A continuous wave Doppler interrogation of the area demonstrated a gradient of ≈ 25 mmHg [Figure 6B]. 2-dimensional transthoracic echocardiography interrogation in the subcostal view identified the etiology of the left ventricular outflow tract obstruction [Figure 7, Videoclip-2]. What is the diagnosis? Figure 2Transthoracic echocardiography image showing the relationship between the pulmonary artery and the left ventricle. View Large Image Figure Viewer Download Hi-res image Figure 3Subcostal 4-chamber transthoracic echocardiography image showing the perimembranous ventricular septal defect. View Large Image Figure Viewer Download Hi-res image Figure 4A&B. Parasternal long axis transthoracic echocardiography 2-dimensional image showing the obstruction in the left ventricular outflow tract ‘white arrow’ [A], and turbulence in the outflow tract by a color Doppler blood flow map ‘white arrow’[B]. View Large Image Figure Viewer Download Hi-res image Figure 5Subcostal transthoracic echocardiography image showing color Doppler flow acceleration over the left ventricular outflow tract and a ventricular septal defect. View Large Image Figure Viewer Download Hi-res image Figure 6A&B. Subcostal transthoracic echocardiography image showing the width of the obstruction [A] and the pressure gradient across the obstruction [B]. View Large Image Figure Viewer Download Hi-res image Figure 7A subcostal transthoracic echocardiography view showing the etiology of the left ventricular outflow tract obstruction in systole. View Large Image Figure Viewer Download Hi-res image

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Evaluation of 3D stack-of-spiral turbo FLASH acquisitions for pseudo-continuous and velocity-selective ASL-derived brain perfusion mapping.

The most-used 3D acquisitions for ASL are gradient and spin echo (GRASE)- and stack-of-spiral (SOS)-based fast spin echo, which require multiple shots. Alternatively, turbo FLASH (TFL) allows longer echo trains, and SOS-TFL has the potential to reduce the number of shots to even single-shot, thus improving the temporal resolution. Here we compare the performance of 3D SOS-TFL and 3D GRASE for ASL at 3T. The 3D SOS-TFL readout was optimized with respect to fat suppression and excitation flip angles for pseudo-continuous ASL- and velocity-selective (VS)ASL-derived cerebral blood flow (CBF) mapping as well as for VSASL-derived cerebral blood volume (CBV) mapping. Results were compared with 3D GRASE readout on healthy volunteers in terms of perfusion quantification and temporal SNR (tSNR) efficiency. CBF and CBV mapping derived from 3D SOS-TFL-based ASL was demonstrated on one stroke patient, and the potential for single-shot acquisitions was exemplified. SOS-TFL with a 15° flip angle resulted in adequate tSNR efficiency with negligible image blurring. Selective water excitation was necessary to eliminate fat-induced artifacts. For pseudo-continuous ASL- and VSASL-based CBF and CBV mapping, compared to the employed four-shot 3D GRASE with an acceleration factor of 2, the fully sampled 3D SOS-TFL delivered comparable performance (with a similar scan time) using three shots, which could be further undersampled to achieve single-shot acquisition with higher tSNR efficiency. SOS-TFL had reduced CSF contamination for VSASL-CBF. 3D SOS-TFL acquisition was found to be a viable substitute for 3D GRASE for ASL with sufficient tSNR efficiency, minimal relaxation-induced blurring, reduced CSF contamination, and the potential of single-shot, especially for VSASL.

Multi-mode fiber-based speckle contrast optical spectroscopy: analysis of speckle statistics.

Speckle contrast optical spectroscopy/tomography (SCOS/T) provides a real-time, non-invasive, and cost-efficient optical imaging approach to mapping of cerebral blood flow. By measuring many speckles (n>>10), SCOS/T has an increased signal-to-noise ratio relative to diffuse correlation spectroscopy, which measures one or a few speckles. However, the current free-space SCOS/T designs are not ideal for large field-of-view imaging in humans because the curved head contour cannot be readily imaged with a single flat sensor and hair obstructs optical access. Herein, we evaluate the feasibility of using cost-efficient multi-mode fiber (MMF) bundles for use in SCOS/T systems. One challenge with speckle contrast measurements is the potential for confounding noise sources (e.g., shot noise, readout noise) which contribute to the standard deviation measure and corrupt the speckle contrast measure that is central to the SCOS/T systems. However, for true speckle measurements, the histogram of pixel intensities from light interference follows a non-Gaussian distribution, specifically a gamma distribution with non-zero skew, whereas most noise sources have pixel intensity distributions that are Gaussian. By evaluating speckle data from static and dynamic targets imaged through an MMF, we use histograms and statistical analysis of pixel histograms to evaluate whether the statistical properties of the speckles are retained. We show that flow-based speckle can be distinguished from static speckle and from sources of system noise through measures of skew in the pixel intensity histograms. Finally, we illustrate in humans that MMF bundles relay blood flow information.

Comparison and optimization of pCASL and VSASL for rat thoracolumbar spinal cord MRI at 9.4T.

To evaluate pseudo-continuous arterial spin labeling (pCASL) and velocity-selective arterial spin labeling (VSASL) for quantification of spinal cord blood flow (SCBF) in the rat thoracolumbar spinal cord. Labeling efficiency (LE) was compared between pCASL and three VSASL variants in simulations and both phantom and in vivo experiments at 9.4T. For pCASL, the effects of label plane position and shimming were systematically evaluated. For VSASL, the effects of composite pulses and phase cycling were evaluated to reduce artifacts. Additionally, vessel suppression, respiratory, and cardiac gating were evaluated to reduce motion artifacts. pCASL and VSASL maps of spinal cord blood flow were acquired with the optimized protocols. LE of the descending aorta was larger in pCASL compared to VSASL variants. In pCASL, LE off-isocenter was improved by local shimming positioned at the label plane and the anatomical level of labeling for the thoracic cord was only viable at the level of the T10 vertebra. Cardiac gating was essential to reduce motion artifacts. Both pCASL and VSASL successfully demonstrated comparable SCBF values in the thoracolumbar cord. pCASL demonstrated high and consistent LE in the thoracic aorta, and VSASL was also feasible, but with reduced efficiency. A combination of cardiac gating and recording of actual post-label delays was important for accurate SCBF quantification. These results highlight the challenges and solutions to achieve sufficient ASL labeling and contrast at high field in organs prone to motion.

Thin-film optical-acoustic combiner enables high-speed wide-field multi-parametric photoacoustic microscopy in reflection mode.

Multi-parametric photoacoustic microscopy (PAM) is uniquely capable of simultaneous high-resolution mapping of blood oxygenation and flow in vivo. However, its speed has been limited by the dense sampling required for blood flow quantification. To overcome this limitation, we have developed a high-speed multi-parametric PAM system, which enables simultaneous acquisition of ∼500 densely sampled B-scans by superposing the rapid optical scanning across the line-shaped focus of a cylindrically focused ultrasonic transducer over the conventional mechanical scan of the optical-acoustic dual foci. A novel, to the best of our knowledge, optical-acoustic combiner (OAC) is designed and implemented to accommodate the short working distance of the transducer, enabling convenient confocal alignment of the dual foci in reflection mode. A resonant galvanometer (GM) provides stabilized high-speed large-angle scanning. This new system can continuously monitor microvascular blood oxygenation (sO2) and flow over a 4.5 × 3 mm2 area in the awake mouse brain with high spatial and temporal resolutions (6.9 µm and 0.3 Hz, respectively).