Isotropic Spatial Resolution Research Articles

An optimized MP2RAGE sequence for studying both brain and cervical spinal cord in a single acquisition at 3T

Magnetization Prepared 2 Rapid Acquisition Gradient Echo (MP2RAGE) is a T1 mapping technique that has been used broadly on brain and recently on cervical spinal cord (cSC).The growing interest for combined investigation of brain and SC in numerous pathologies of the central nervous system such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and traumatic injuries, now brings about the need for optimization with regards to this specific investigation. This implies large spatial coverage with high spatial resolution and short acquisition time, high CNR and low B1+ sensitivity, as well as high reproducibility and robust post-processing tools for T1 quantification in different regions of brain and SC.In this work, a dedicated protocol (referred to as Pr-BSC) has been optimized for simultaneous brain and cSC T1 MP2RAGE acquisition at 3T. After computer simulation optimization, the protocol was applied for in vivo validation experiments and compared to previously published state of the art protocols focusing on either the brain (Pr-B) or the cSC (Pr-SC). Reproducibility and in-ROI standard deviations were assessed on healthy volunteers in the perspective of future clinical use.The mean T1 values, obtained by the Pr-BSC, in brain white, gray and deep gray matters were: (mean ± in-ROI SD) 792 ± 27 ms, 1339 ± 139 ms and 1136 ± 88 ms, respectively. In cSC, T1 values for white matter corticospinal, posterior sensory, lateral sensory and rubro/reticulospinal tracts were 902 ± 41 ms, 920 ± 35 ms, 903 ± 46 ms, 891 ± 41 ms, respectively, and 954 ± 32 ms for anterior and intermediate gray matter. The Pr-BSC protocol showed excellent agreement with previously proposed Pr-B on brain and Pr-SC on cSC, with very high inter-scan reproducibility (coefficients of variation of 0.52 ± 0.36% and 1.12 ± 0.62% on brain and cSC, respectively).This optimized protocol covering both brain and cSC with a sub-millimetric isotropic spatial resolution in one acquisition of less than 8 min, opens up great perspectives for clinical applications focusing on degenerative tissue such as encountered in MS and ALS.

Coronary Flow Assessment Using Accelerated 4D Flow MRI With Respiratory Motion Correction.

Magnetic resonance imaging (MRI) can potentially be used for non-invasive screening of patients with stable angina pectoris to identify probable obstructive coronary artery disease. MRI-based coronary blood flow quantification has to date only been performed in a 2D fashion, limiting its clinical applicability. In this study, we propose a framework for coronary blood flow quantification using accelerated 4D flow MRI with respiratory motion correction and compressed sensing image reconstruction. We investigate its feasibility and repeatability in healthy subjects at rest. Fourteen healthy subjects received 8 times-accelerated 4D flow MRI covering the left coronary artery (LCA) with an isotropic spatial resolution of 1.0 mm3. Respiratory motion correction was performed based on 1) lung-liver navigator signal, 2) real-time monitoring of foot-head motion of the liver and LCA by a separate acquisition, and 3) rigid image registration to correct for anterior-posterior motion. Time-averaged diastolic LCA flow was determined, as well as time-averaged diastolic maximal velocity (VMAX) and diastolic peak velocity (VPEAK). 2D flow MRI scans of the LCA were acquired for reference. Scan-rescan repeatability and agreement between 4D flow MRI and 2D flow MRI were assessed in terms of concordance correlation coefficient (CCC) and coefficient of variation (CV). The protocol resulted in good visibility of the LCA in 11 out of 14 subjects (six female, five male, aged 28 ± 4 years). The other 3 subjects were excluded from analysis. Time-averaged diastolic LCA flow measured by 4D flow MRI was 1.30 ± 0.39 ml/s and demonstrated good scan-rescan repeatability (CCC/CV = 0.79/20.4%). Time-averaged diastolic VMAX (17.2 ± 3.0 cm/s) and diastolic VPEAK (24.4 ± 6.5 cm/s) demonstrated moderate repeatability (CCC/CV = 0.52/19.0% and 0.68/23.0%, respectively). 4D flow- and 2D flow-based diastolic LCA flow agreed well (CCC/CV = 0.75/20.1%). Agreement between 4D flow MRI and 2D flow MRI was moderate for both diastolic VMAX and VPEAK (CCC/CV = 0.68/20.3% and 0.53/27.0%, respectively). In conclusion, the proposed framework of accelerated 4D flow MRI equipped with respiratory motion correction and compressed sensing image reconstruction enables repeatable diastolic LCA flow quantification that agrees well with 2D flow MRI.

A multicontrast MR atlas of the Wistar rat brain

Abstract We describe a multi-contrast, multi-dimensional atlas of the Wistar rat acquired at microscopic spatial resolution using magnetic resonance histology (MRH). Diffusion weighted images, and associated scalar images were acquired of a single specimen with a fully sampled Fourier reconstruction, 61 angles and b=3000 s/mm2 yielding 50 um isotropic spatial resolution. The higher angular sampling allows use of the GQI algorithm improving the angular invariance of the scalar images and yielding an orientation distribution function to assist in delineating subtle boundaries where there are crossing fibers and track density images providing insight into local fiber architecture. A multigradient echo image of the same specimen was acquired at 25 um isotropic spatial resolution. A quantitative susceptibility map enhances fiber architecture relative to the magnitude images. An accompanying multi-specimen atlas (n=6) was acquired with compressed sensing with the same diffusion protocol as used for the single specimen atlas. An average was created using diffeomorphic mapping. Scalar volumes from the diffusion data, a T2* weighted volume, a quantitative susceptibility map, and a track density volume, all registered to the same space provide multiple contrasts to assist in anatomic delineation. The new template provides significantly increased contrast in the scalar DTI images when compared to previous atlases. A compact interactive viewer based on 3D Slicer is provided to facilitate comparison among the contrasts in the multiple volumes. The single volume and average atlas with multiple 3D volumes provide an improved template for anatomic interrogation of the Wistar rat brain. The improved contrast to noise in the scalar DTI images and the addition of other volumes (eg. QA,QSM,TDI ) will facilitate automated label registration for MR histology and preclinical imaging.

Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Reactive oxygen FIB spin milling enables correlative workflow for 3D super-resolution light microscopy and serial FIB/SEM of cultured cells

Correlative light and electron microscopy (CLEM) is a powerful tool for defining the ultrastructural context of molecularly-labeled biological specimens, particularly when superresolution fluorescence microscopy (SRM) is used for CLEM. Current CLEM, however, is limited by the stark differences in sample preparation requirements between the two modalities. For CLEM using SRM, the small region of interest (ROI) of either or both modalities also leads to low success rate and imaging throughput. To overcome these limitations, here we present a CLEM workflow based on a novel focused ion beam/scanning electron microscope (FIB/SEM) compatible with common SRM for imaging biological specimen with ultrahigh 3D resolution and improved imaging throughput. By using a reactive oxygen source in a plasma FIB (PFIB) and a rotating sample stage, the novel FIB/SEM was able to achieve several hundreds of micrometer large area 3D analysis of resin embedded cells through a process named oxygen serial spin mill (OSSM). Compared with current FIB mechanisms, OSSM offers gentle erosion, highly consistent slice thickness, reduced charging during SEM imaging, and improved SEM contrast without increasing the dose of post-staining and fixation. These characteristics of OSSM-SEM allowed us to pair it with interferometric photoactivated localization microscopy (iPALM), a recent SRM technique that affords 10–20 nm isotropic spatial resolution on hydrated samples, for 3D CLEM imaging. We demonstrate a CLEM workflow generalizable to using other SRM strategies using mitochondria in human osteosarcoma (U2OS) cells as a model system, where immunostained TOM20, a marker for the mitochondrial outer membrane, was used for iPALM. Owing to the large scan area of OSSM-SEM, it is now possible to select as many FOVs as needed for iPALM and conveniently re-locate them in EM, this improving the imaging throughput. The significantly reduced dose of post-fixation also helped to better preserve the sample ultrastructures as evidenced by the excellent 3D registration between OSSM-SEM and iPALM images and by the accurate localization of TOM20 (by iPALM) to the peripheries of mitochondria (by OSSM-SEM). These advantages make OSSM-SEM an ideal modality for CLEM applications. As OSSM-SEM is still in development, we also discuss some of the remaining issues and the implications to biological imaging with SEM alone or with CLEM.

Musculoskeletal 3D MRI: A Decade of Developments and Innovations Coming to Fruition.

Three-dimensional magnetic resonance imaging (3D MRI) with isotropic high spatial resolution data sets has advanced into a key technology for multiple advanced musculoskeletal (MSK) imaging applications, such as dynamic multiplanar evaluation of small and complex anatomical structures, curved multiplanar reformation of long-winded structures (e.g., nerves and tendons), the realization of efficient joint and whole-body MRI protocols, and advanced MR image reformations, including the creation of cartilage maps, as well as volume rendering and cinematic rendering-type 3D MR images.[1] [2] [3]

Comprehensive ultrahigh resolution whole brain in vivo MRI dataset as a human phantom

Here, we present an extension to our previously published structural ultrahigh resolution T1-weighted magnetic resonance imaging (MRI) dataset with an isotropic resolution of 250 µm, consisting of multiple additional ultrahigh resolution contrasts. Included are up to 150 µm Time-of-Flight angiography, an updated 250 µm structural T1-weighted reconstruction, 330 µm quantitative susceptibility mapping, up to 450 µm structural T2-weighted imaging, 700 µm T1-weighted back-to-back scans, 800 µm diffusion tensor imaging, one hour continuous resting-state functional MRI with an isotropic spatial resolution of 1.8 mm as well as more than 120 other structural T1-weighted volumes together with multiple corresponding proton density weighted acquisitions collected over ten years. All data are from the same participant and were acquired on the same 7 T scanner. The repository contains the unprocessed data as well as (pre-)processing results. The data were acquired in multiple studies with individual goals. This is a unique and comprehensive collection comprising a “human phantom” dataset. Therefore, we compiled, processed, and structured the data, making them publicly available for further investigation.

Respiratory motion correction for enhanced quantification of hepatic lesions in simultaneous PET and DCE-MR imaging

Simultaneous positron-emission tomography (PET)-magnetic resonance (MR) imaging is a hybrid technique in oncological hepatic imaging combining soft-tissue and functional contrast of dynamic contrast enhanced MR (DCE-MR) with metabolic information from PET. In this context, respiratory motion represents a major challenge by introducing blurring, artifacts and misregistration in the liver. In this work, we propose a free-breathing 3D non-rigid respiratory motion correction framework for simultaneously acquired DCE-MR and PET data, which makes use of higher spatial resolution MR data to derive motion information used directly during image reconstruction to minimize image blurring and motion artifacts. The main aim was to increase contrast of hepatic metastases to improve their detection and characterization. DCE-MR data were acquired at 3T through a golden radial phase encoding scheme, enabling derivation of motion fields. These were used in the motion compensated image reconstruction of DCE-MR time-series (48 time-points, 6 s temporal resolution, 1.5 mm isotropic spatial resolution) and 3D PET activity map, which was subsequently interpolated to the DCE-MR resolution. The extended Tofts model was fitted to DCE-MR data, obtaining functional parametric maps related to perfusion such as the endothelial permeability (). Fifty-seven hepatic metastases were identified and analyzed. Quantitative evaluations of motion correction in PET images demonstrated average percentage increases of 16% ± 5% (mean ± SD) in Contrast (C), 18% ± 6% in SUVmean and 14% ± 2% in SUVmax, while DCE-MR and scored contrast-to-noise-ratio increases of 64% ± 3% and 90% ± 6%, respectively. Motion-corrected data visually showed improved image contrast of hepatic metastases and effectively reduced blurring and motion artefacts. Scatter plots of SUVmean versus suggested that the proposed framework improved differentiation of measurements. The presented motion correction framework for simultaneously acquired PET-DCE-MR data provides accurately aligned images with increased contrast of hepatic lesions allowing for improved detection and characterization.

Sub-millimetre resolution laminar fMRI using Arterial Spin Labelling in humans at 7 T.

Laminar fMRI at ultra-high magnetic field strength is typically carried out using the Blood Oxygenation Level-Dependent (BOLD) contrast. Despite its unrivalled sensitivity to detecting activation, the BOLD contrast is limited in its spatial specificity due to signals stemming from intra-cortical ascending and pial veins. Alternatively, regional changes in perfusion (i.e., cerebral blood flow through tissue) are colocalised to neuronal activation, which can be non-invasively measured using Arterial Spin Labelling (ASL) MRI. In addition, ASL provides a quantitative marker of neuronal activation in terms of perfusion signal, which is simultaneously acquired along with the BOLD signal. However, ASL for laminar imaging is challenging due to the lower SNR of the perfusion signal and higher RF power deposition i.e., specific absorption rate (SAR) of ASL sequences. In the present study, we present for the first time in humans, isotropic sub-millimetre spatial resolution functional perfusion images using Flow-sensitive Alternating Inversion Recovery (FAIR) ASL with a 3D-EPI readout at 7 T. We show that robust statistical activation maps can be obtained with perfusion-weighting in a single session. We observed the characteristic BOLD amplitude increase towards the superficial laminae, and, in apparent discrepancy, the relative perfusion profile shows a decrease of the amplitude and the absolute perfusion profile a much smaller increase towards the cortical surface. Considering the draining vein effect on the BOLD signal using model-based spatial “convolution”, we show that the empirically measured perfusion and BOLD profiles are, in fact, consistent with each other. This study demonstrates that laminar perfusion fMRI in humans is feasible at 7 T and that caution must be exercised when interpreting BOLD signal laminar profiles as direct representation of the cortical distribution of neuronal activity.

Improved cortical surface reconstruction using sub-millimeter resolution MPRAGE by image denoising

Automatic cerebral cortical surface reconstruction is a useful tool for cortical anatomy quantification, analysis and visualization. Recently, the Human Connectome Project and several studies have shown the advantages of using T1-weighted magnetic resonance (MR) images with sub-millimeter isotropic spatial resolution instead of the standard 1-mm isotropic resolution for improved accuracy of cortical surface positioning and thickness estimation. Nonetheless, sub-millimeter resolution images are noisy by nature and require averaging multiple repetitions to increase the signal-to-noise ratio for precisely delineating the cortical boundary. The prolonged acquisition time and potential motion artifacts pose significant barriers to the wide adoption of cortical surface reconstruction at sub-millimeter resolution for a broad range of neuroscientific and clinical applications. We address this challenge by evaluating the cortical surface reconstruction resulting from denoised single-repetition sub-millimeter T1-weighted images. We systematically characterized the effects of image denoising on empirical data acquired at 0.6 mm isotropic resolution using three classical denoising methods, including denoising convolutional neural network (DnCNN), block-matching and 4-dimensional filtering (BM4D) and adaptive optimized non-local means (AONLM). The denoised single-repetition images were found to be highly similar to 6-repetition averaged images, with a low whole-brain averaged mean absolute difference of ~0.016, high whole-brain averaged peak signal-to-noise ratio of ~33.5 dB and structural similarity index of ~0.92, and minimal gray matter–white matter contrast loss (2% to 9%). The whole-brain mean absolute discrepancies in gray matter–white matter surface placement, gray matter–cerebrospinal fluid surface placement and cortical thickness estimation were lower than 165 μm, 155 μm and 145 μm—sufficiently accurate for most applications. These discrepancies were approximately one third to half of those from 1-mm isotropic resolution data. The denoising performance was equivalent to averaging ~2.5 repetitions of the data in terms of image similarity, and 1.6–2.2 repetitions in terms of the cortical surface placement accuracy. The scan-rescan variability of the cortical surface positioning and thickness estimation was lower than 170 μm. Our unique dataset and systematic characterization support the use of denoising methods for improved cortical surface reconstruction at sub-millimeter resolution.

The Napkin-Ring Sign – the Story Behind Invasive Coronary Angiography

Abstract Coronary artery disease (CAD) represents one of the leading causes of morbidity and mortality across Europe. Most of the patients do not experience any warning sign before the coronary event develops, therefore screening this group of patients is essential to prevent major cardiac events. Coronary computed tomography angiography (CCTA) offers a noninvasive approach of the coronary arteries, providing information not only on the presence and severity of the coronary stenosis, but is also able to characterize the structure of the coronary wall. CCTA allows complex evaluation of the extension of CAD, and by assessing the structure of the atherosclerotic plaque, it can identify its degree of vulnerability. The napkin-ring sign (NRS) represents a ring-like attenuation of the non-calcified portion of the coronary lesion and has a high specificity (96–100%) for the identification of thin cap fibroatheroma (TCFA) or culprit lesion in acute coronary syndromes (ACS). It is also an independent predictor for ACS events and the strongest predictor for future ACS. Modern CCTA can provide submillimeter isotropic spatial resolution. Thus, CT attenuation-based tissue interpretation enables the assessment of total coronary plaque burden and individual plaque components, with a similar accuracy as intravascular ultrasoud-based investigations. This review aims to present the important role of CCTA as a potent screening tool for patients with CAD, and the current evidences in the detection and quantification of vulnerable plaques.

3D MRI of explanted sheep hearts with submillimeter isotropic spatial resolution: comparison between diffusion tensor and structure tensor imaging

ObjectiveThe aim of the study is to compare structure tensor imaging (STI) with diffusion tensor imaging (DTI) of the sheep heart (approximately the same size as the human heart).Materials and methodsMRI acquisition on three sheep ex vivo hearts was performed at 9.4 T/30 cm with a seven-element RF coil. 3D FLASH with an isotropic resolution of 150 µm and 3D spin-echo DTI at 600 µm were performed. Tensor analysis, angles extraction and segments divisions were performed on both volumes.ResultsA 3D FLASH allows for visualization of the detailed structure of the left and right ventricles. The helix angle determined using DTI and STI exhibited a smooth transmural change from the endocardium to the epicardium. Both the helix and transverse angles were similar between techniques. Sheetlet organization exhibited the same pattern in both acquisitions, but local angle differences were seen and identified in 17 segments representation.DiscussionThis study demonstrated the feasibility of high-resolution MRI for studying the myocyte and myolaminar architecture of sheep hearts. We presented the results of STI on three whole sheep ex vivo hearts and demonstrated a good correspondence between DTI and STI.

Carotid artery wall imaging using 7.0T magnetic resonance imaging with threedimensional DANTE-prepared FLASH in ApoE-/- mice

To explore the feasibility of three-dimensional (3D) vessel wall imaging of carotid atherosclerotic plaques in ApoE-/- mice using 7.0T magnetic resonance imaging (MRI) with delays alternating with nutations for tailored excitation (DANTE)-prepared fast low-angle shot (DANTE-FLASH) technique. Numerical simulations were performed for optimizing imaging parameters to maximize the wall-lumen contrast. Six ApoE-/- and three wild-type mice were scanned using a 7.0T MRI scanner with DANTE-FLASH and multi-slice 2D RARE coupled with inflow outflow saturation bands (2D-IOSBRARE). The wall signal-to-noise ratio (SNRwall), lumen SNR (SNRlumen), wall-lumen contrast-to-noise ratio (CNR), lumen area (LA), and wall area (WA) were compared between DANTE- FLASH and 2D-IOSB-RARE sequences. Linear regression analysis was performed to assess the correlation between the MRI measurements and histopathological measurements of LA and WA. Based on the simulation results, a flip angle of 15° and a train length of 150 were implemented in the live imaging study. Compared with 2D-IOSB-RARE, DANTE-FLASH provided a slightly reduced CNR (P < 0.001) but much improved slice resolution. The LA and WA measurements from the DANTE-FLASH and 2D-IOSB- RARE showed excellent agreement based on ICC analysis (LA: ICC=0.94, P < 0.001; WA: ICC=0.93, P < 0.001) and Bland-Altman plots. Strong correlations were observed between the MRI and histopathological measurements for both LA (P < 0.0001) and WA (P < 0.0001). As a 3D black-blood MR sequence, DANTE-FLASH provides isotropic high spatial resolution to allow reliable visualization and quantitative evaluation of the arteriosclerotic lesions within the carotid artery of ApoE-/- mice using a 7.0T MRI scanner.

Submicron spatial resolution optical coherence tomography for visualising the 3D structures of cells cultivated in complex culture systems

Three-dimensional (3D) configuration of in vitro cultivated cells has been recognised as a valuable tool in developing stem cell and cancer cell therapy. However, currently available imaging approaches for live cells have drawbacks, including unsatisfactory resolution, lack of cross-sectional and 3D images, and poor penetration of multi-layered cell products, especially when cells are cultivated on semitransparent carriers. Herein, we report a prototype of a full-field optical coherence tomography (FF-OCT) system with isotropic submicron spatial resolution in en face and cross-sectional views that provides a label-free, non-invasive platform with high-resolution 3D imaging. We validated the imaging power of this prototype by examining (1) cultivated neuron cells (N2A cell line); (2) multilayered, cultivated limbal epithelial sheets (mCLESs); (3) neuron cells (N2A cell line) and mCLESs cultivated on a semitransparent amniotic membrane (stAM); and (4) directly adherent colonies of neuron-like cells (DACNs) covered by limbal epithelial cell sheets. Our FF-OCT exhibited a penetrance of up to 150 μm in a multilayered cell sheet and displayed the morphological differences of neurons and epithelial cells in complex coculture systems. This FF-OCT is expected to facilitate the visualisation of cultivated cell products in vitro and has a high potential for cell therapy and translational medicine research.

Characterizing pore-scale structure-flow correlations in sedimentary rocks using magnetic resonance imaging.

Quantitative, three-dimensional (3D) spatially resolved magnetic resonance flow imaging (flow MRI) methods are presented to characterize structure-flow correlations in a 4-mm-diameter plug of Ketton limestone rock using undersampled k- and q-space data acquisition methods combined with compressed sensing (CS) data reconstruction techniques. The acquired MRI data are coregistered with an X-ray microcomputed tomography (μCT) image of the same rock sample, allowing direct correlation of the structural features of the rock with local fluid transport characteristics. First, 3D velocity maps acquired at 35 μm isotropic spatial resolution showed that the flow was highly heterogeneous, with ∼10% of the pores carrying more than 50% of the flow. Structure-flow correlations were found between the local flow velocities through pores and the size and topology (coordination number) associated with these pores. These data show consistent trends with analogous data acquired for flow through a packing of 4-mm-diameter spheres, which may be due to the microstructure of Ketton rock being a consolidation of approximately spherical grains. Using two-dimensional and 3D visualization of coregistered μCT images and velocity maps, complex pore-scale flow patterns were identified. Second, 3D spatially resolved propagators were acquired at 94 μm isotropic spatial resolution. Flow dispersion within the rock was examined by analyzing each of the 331 776 local propagators as a function of observation time. Again, the heterogeneity of flow within the rock was shown. Quantification of the mean and standard deviation of each of the local propagators showed enhanced mixing occurring within the pore space at longer observation times. These spatially resolved measurements also enable investigation of the length scale of a representative elementary volume. It is shown that for a 4-mm-diameter plug this length scale is not reached.

High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.

Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy

Rapid 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale high-resolution mapping of entire macro-scale organs. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our approach yields 3D images with high, isotropic spatial resolution and rapid acquisition over two-order-of-magnitude faster than conventional 3D microscopy implementations. We demonstrate the imaging of whole brain (~400 mm3), entire gastrocnemius and tibialis muscles (~200 mm3) of mouse at ultra-high throughput of 5~10 min per sample and post-improved subcellular resolution of ~ 1.5 μm (0.5-μm iso-voxel size). Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, are also readily accomplished by our method.

Diffusion biomarkers in chronic myocardial infarction.

Cardiac diffusion tensor magnetic resonance imaging (cDTI) allows estimating the aggregate cardiomyocyte architecture in healthy subjects and its remodeling as a result of cardiac disease. In this study, cDTI was used to quantify microstructural changes occurring in swine (N=7) six to ten weeks after myocardial infarction. Each heart was extracted and imaged ex vivo with 1mm isotropic spatial resolution. Microstructural changes were quantified in the border zone and infarct region by comparing diffusion tensor invariants - fractional anisotropy (FA), mode, and mean diffusivity (MD) - radial diffusivity, and diffusion tensor eigenvalues with the corresponding values in the remote myocardium. MD and radial diffusivity increased in the infarct and border regions with respect to the remote myocardium (p<0.01). In contrast, FA and mode decreased in the infarct and border regions (p<0.01). Diffusion tensor eigenvalues also increased in the infarct and border regions, with a larger increase in the secondary and tertiary eigenvalues.

Ultra-high resolution, 3-dimensional magnetic resonance imaging of the atherosclerotic vessel wall at clinical 7T.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3–80.1)%, and a median CNR gain of +68.1 (38.5–95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.

Line-field confocal optical coherence tomography for three-dimensional skin imaging.

This paper reports on the latest advances in line-field confocal optical coherence tomography (LC-OCT), a recently invented imaging technology that now allows the generation of either horizontal (x × y) section images at an adjustable depth or vertical (x × z) section images at an adjustable lateral position, as well as three-dimensional images. For both two-dimensional imaging modes, images are acquired in real-time, with real-time control of the depth and lateral positions. Three-dimensional (x × y × z) images are acquired from a stack of horizontal section images. The device is in the form of a portable probe. The handle of the probe has a button and a scroll wheel allowing the user to control the imaging modes. Using a supercontinuum laser as a broadband light source and a high numerical microscope objective, an isotropic spatial resolution of ∼1 µm is achieved. The field of view of the three-dimensional images is 1.2 mm × 0.5 mm × 0.5 mm (x × y × z). Images of skin tissues are presented to demonstrate the potential of the technology in dermatology.