All MRI scans were performed with informed consent from volunteers as part of a study approved by our institutional research ethics board.
NOTE: The methods described below have been used on a 3T MRI system. The acquisition is performed using a radial phase contrast MRI sequence. This sequence was prepared by modifying the readout trajectory (to achieve a stellate pattern) of the manufacturer&#39;s Cartesian phase contrast MRI. The sequence and sample protocols are available upon request through our C2P exchange platform. All reconstructions in this work were performed on a standard desktop computer with the following specifications: 32 GB memory, 3.40 GHz processor with 8 cores, and 2GB graphic card with 1024 compute unified device architecture (CUDA) cores. Image reconstruction was performed on MATLAB. Nonuniform fast Fourier transform (NUFFT)29&#160;was performed on the graphics processing unit (GPU). Motion correction parameters were calculated using elastix30.&#160;Figure 1&#160;depicts the protocol in a chronological order, tracking how the acquired velocity encodes (color coded in&#160;Figure 1) are processed with representative images at each stage of reconstruction. The reconstruction code is available at https://github.com/datta-g/Fetal_PC_MRI. While we provide the steps in the protocol here, most of these algorithm steps are automated in our pipeline.
1.&#160;Subject positioning and localizer exams
<ol>
	<li>Assist the mother in positioning herself on the MRI table in her preferred comfortable position, usually supine or lateral decubitus positions, for the MRI exam.</li>
	<li>Place the cardiac coil over the abdominal region of the mother.</li>
	<li>Load the MRI table in the magnet bore and notify the mother that the scan is about to start.</li>
	<li>Run a localizer exam to locate the fetal body (resolution: 0.9 x 0.9 x 10 mm3, TE/TR: 5.0/15.0 ms, FOV: 450 x 450 mm2, slices: 6).</li>
	<li>Run a refined localizer exam to locate the fetal vasculature with the slice group centered on the fetal heart (resolution 1.1 x 1.1 x 6.0 mm3, TE/TR: 2.69/1335.4 ms, FOV: 350 x 350 mm2, slices: 10, orientation: axial to fetus).</li>
	<li>Repeat the refined localizers with sagittal and coronal orientations for a clearer view of the fetal vessels.</li>
	<li>Repeat the refined localizers in cases of gross fetal motion.</li>
</ol>
2.&#160;Acquisition of fetal blood flow data
<ol>
	<li>Locate fetal vessels using the localizer exams. For example, the descending aorta is a long straight vessel near the spine in the sagittal planes. The ascending aorta and main pulmonary arteries can be identified as vessels leaving the left and right ventricles, respectively. The ductus arteriosus can be tracked as a downstream segment of the main pulmonary artery proximal to the descending aorta. The superior vena cava can be identified from axial planes near the base of the fetal heart as the vessel adjacent to the ascending aorta.</li>
	<li>Prescribe a slice perpendicular to the axis of the fetal vessel of interest. Rotate and move the slice guideline on the MRI console computer such that it intersects the target vessel perpendicularly.</li>
	<li>Set the scan parameters (acquisition type: radial phase contrast MRI, resolution: 1.3 x 1.3 x 5.0 mm3, echo time (TE)/ repetition time (TR): 3.25/5.75 ms, field-of-view (FOV): 240 x 240 mm2, slice: 1, velocity encoding: 100-150 cm/s depending on vessel of interest, velocity encoding direction: through plane, radial views: 1500 per encode, free breathing).</li>
	<li>Run the scan and verify the prescription based on the initial time-averaged reconstruction performed and displayed on the MRI console computer. Repeat the localizer and phase contrast scans if the target vessel is absent or unidentifiable from the initial reconstruction. Acquired raw data is represented in the schematic in&#160;Figure 1A&#160;with the velocity compensated and through plane acquisitions color coded as red and blue, respectively.</li>
	<li>Repeat the fetal blood flow data acquisition for each target blood vessel. 
	NOTE: The acquired raw data (format: DAT files) must be transferred for offline reconstruction. For example, on Siemens scanners, this can be performed by running &#39;twix&#39;. The acquired raw data is right clicked from the list acquisitions and &#34;copy total raid file&#34; is chosen.</li>
</ol>
3.&#160;Motion correction of fetal measurements
<ol>
	<li>Reconstruct real-time series (temporal resolution: 370 ms, radial views: 64) from the acquired data using CS with 15 iterations of a conjugate gradient descent optimization exploiting spatial total variation (STV, weight: 0.008) and temporal total variation (TTV, weight: 0.08) regularization as represented by the schematic in&#160;Figure 1B.</li>
	<li>Select a region of interest (ROI) encompassing the vessel of interest from this first real-time reconstruction using a graphic user interface developed in MATLAB. In this step, the user must draw a contour that encloses the fetal anatomy, such as the target great vessels or the fetal heart.</li>
	<li>Perform rigid-body motion tracking with elastix30&#160;(based on normalized mutual information with empirically optimized parameters: 4 pyramid levels, 300 iterations and translational transforms).</li>
	<li>Reject tracked real-time frames that share low mutual information (MI) with all other frames (whereby MI is less than 1.5x the interquartile range from the mean MI). These frames are deemed to be represented through plane motion or gross fetal motion.</li>
	<li>Use the MRI data corresponding to the longest series of continuous real-time frames (without gaps) from the remaining frames as the quiescent period used for further reconstruction.</li>
	<li>Interpolate translational motion correction parameters from the temporal resolution of the real-time series (370 ms) to the TR of the quiescent acquisition (5.75 ms).</li>
	<li>Apply interpolated parameters to the defined quiescent period of the MRI data by modulating the phase as in: 
	<img alt="Equation 1" src="/files/ftp_upload/61953/61953_eq01.png" /> 
	 
	where&#160;s&#39;&#160;is the motion corrected data,&#160;kx&#160;and&#160;ky&#160;are the coordinates in k-space,&#160;s&#160;is the acquired uncorrected data,&#160;&#916;x&#160;and&#160;&#916;y&#160;are the tracked displacements in space, and&#160;j&#160;represents <img alt="Equation 3" src="/files/ftp_upload/61953/61953eq2.jpg" />. 
	NOTE: All numerical values of regularization coefficients in this work were optimized in earlier experiments. This was accomplished using a brute-force grid search to find the regularization coefficients that minimized the error between reconstructions of a highly sampled fetal reference dataset and retrospectively undersampled cases from the same dataset.</li>
</ol>
4.&#160;Solving for fetal heart rate
<ol>
	<li>Reconstruct a second real-time image series at a higher temporal resolution (temporal resolution: 46 ms, radial views: 8) using the acquired data using CS, again with 15 iterations of a conjugate gradient descent optimization with STV (weight: 0.008) and TTV (weight: 0.08) regularization as represented by the schematic in Figure 1C.</li>
	<li>Re-select an ROI encompassing the fetal vessel of interest.</li>
	<li>Run multiparameter MOG on the real-time series to derive the time-dependent fetal heart rate.</li>
	<li>Bin motion corrected MRI data into 15 cardiac phases using the derived heart rate waveform. In this step, the temporal boundaries of the cardiac phases are computed using the heart rate from the previous step. For instance, the boundaries for the&#160;ith&#160;phase in the&#160;kth&#160;heartbeat are given by: 
	<img alt="Equation 2a" src="/files/ftp_upload/61953/61953_eq1a.png" /> 
	<img alt="Equation 2b" src="/files/ftp_upload/61953/61953_eq1b.png" /> 
	where HR(K) is the time at which the&#160;kth&#160;heartbeat occurs. The timestamp of the&#160;nth&#160;radial acquisition is given by (n&#160;x TR). Data with timestamps falling within the boundaries of a cardiac phase are assigned to that phase. 
	NOTE: MOG is a gating technique26&#160;that comprises iterative binning of the acquired data based on a multi-parameter fetal heart rate model to create CINE images that optimize an image metric over a region of interest.</li>
</ol>
5.&#160;Reconstruction of fetal CINEs
<ol>
	<li>Reconstruct fetal flow CINEs using the binned motion corrected MRI data and CS with 10 iterations of a conjugate gradient descent optimization with STV (weight: 0.025) and TTV (weight: 0.01) regularization. Two CINEs are produced at this step: one for the flow compensated acquisition, CFC,&#160;and one with the flow encoded data, CFE, as represented in the schematic in&#160;Figure 1D.</li>
	<li>Compute the velocity image given by the phase of the elementwise product of CFE&#160;and the complex conjugate of CFC.</li>
	<li>Apply background phase correction31&#160;to correct for eddy current effects. Briefly, in this automatic step, a plane is fitted to the phase of static fetal and maternal tissues. The correction is performed by subtracting the plane from the velocity sensitive phase computed in 4.2.</li>
	<li>Write reconstructed data into DICOM files.</li>
	<li>Load DICOMs into flow analysis software, such as Segment v2.232.</li>
	<li>Draw an ROI encompassing the lumen of the blood vessel of interest using the anatomical and velocity sensitive images.</li>
	<li>Propagate the ROI to all cardiac phases and correct for changes in the vessel&#39;s diameter.</li>
	<li>Record flow measurements.</li>
</ol>

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This method enables the non-invasive measurement of blood flow in human fetal great vessels and allows for retrospective motion correction and cardiac gating by making use of iterative reconstruction techniques. Fetal blood flow quantification has been performed with MRI in the past1,3,8,9. These studies had a prospective approach to mitigate motion corruption w...

Comprehensive assessment of the fetal circulation is necessary for monitoring fetal pathologies such as fetal growth restriction (FGR) and congenital heart disease (CHD)1,2,3. In utero, patient management and planning for postnatal care depend on the severity of the fetal pathology4,5,6,7. Feasibility of fetal blood flow quantification with MRI and its applications in assessing fetal pathologies have recently been demonstrated3,8,9. The imaging method, however, faces challenges, such as increased imaging times to achieve high spatiotemporal resolution, lack of cardiac synchronization methods, and unpredictable fetal motion10.
Fetal vasculature comprises small structures (~5 mm diameter for major blood vessels that comprise the descending aorta, ductus arteriosus, ascending aorta, main pulmonary artery, and superior vena cava11,12,13).To resolve these structures and to quantify flow, imaging at high spatial resolution is required. Moreover, the fetal heart rate is about twice that of an adult. A high temporal resolution is thus also required to resolve dynamic cardiac motion and blood flow across the fetal cardiac cycle. Conventional imaging at this high spatiotemporal resolution requires relatively long acquisition times. To address this issue, accelerated fetal MRI14,15,16&#160;has been introduced. Briefly, these acceleration techniques involve undersampling in the frequency domain during data acquisition and retrospective high-fidelity reconstruction using iterative techniques. One such approach is compressed sensing (CS) reconstruction, which allows reconstruction of images from heavily undersampled data when the reconstructed image is sparse in a known domain and undersampling artifacts are incoherent17.
Motion in fetal imaging presents a major challenge. Motion corruption can arise from maternal respiratory motion, maternal bulk motion or gross fetal movement. Maternal respiration leads to periodic translations of the fetus, whereas fetal movements are more complex. Fetal movements can be classified as localized or gross10,18. Localized movements involve motion of only segments of the body. They typically last for about 10-14 s and their frequency increases with gestation (~90 per hour at term)10. These movements generally cause small corruptions and do not affect the imaging area of interest. However, gross fetal movements can lead to severe image corruption with through plane motion components. These movements are whole body movements mediated by the spine and last for 60-90 s.
To avoid artifacts from fetal motion, steps are first taken to minimize maternal motions. Pregnant women are made more relaxed using supportive pillows on the scanner bed and dressed in comfortable gowns and may have their partners present beside the scanner to reduce claustrophobia19,20. To mitigate effects of maternal respiratory motion, studies have performed fetal MR exams under maternal breath-hold21,22,23. However, such acquisitions must be short (~15 s) given the reduced breath-hold tolerance of pregnant subjects. Recently, retrospective motion correction methods have been introduced for fetal MRI14,15,16. These methods track fetal motion using registration toolkits and correct for motion or discard uncorrectable portions of acquired data.
Finally, postnatal cardiac MR images are conventionally acquired using electrocardiogram (ECG) gating to synchronize data acquisition to the cardiac cycle. Without gating, cardiac motion and pulsatile flow from throughout the cardiac cycle are combined, producing artifacts. Unfortunately, the fetal ECG signal suffers from interference from the maternal ECG signal24&#160;and distortions from the magnetic field25. Hence, alternative non-invasive approaches to fetal cardiac gating have been proposed, including self-gating, metric optimized gating (MOG) and doppler ultrasound gating21,26,27,28.
As described in the following sections, our MRI approach to quantify fetal blood flow leverages a novel gating method, MOG, developed in our laboratory and combined with motion correction and iterative reconstruction of accelerated MRI acquisitions. The approach is based on a pipeline in a previously published study14&#160;and is composed of the following five stages: (1) fetal blood flow acquisition, (2) real-time reconstructions, (3) motion correction, (4) cardiac gating, and (5) gated reconstructions.

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			<td>Radial Phase Contrast MRI sequence</td>
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human fetal blood flow quantification with magnetic resonance imaging and motion compensation

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the recognized standard-of-care for blood flow quantification based on phase contrast MRI. While such measurement of blood flow has been possible in adults for decades, methods to extend this capability to fetal blood flow have only recently been developed.
Fetal blood flow quantification in major vessels is important for monitoring fetal pathologies such as congenital heart disease (CHD) and fetal growth restriction (FGR). CHD causes alterations in the cardiac structure and vasculature that change the course of blood in the fetus. In FGR, the path of blood flow is altered through the dilation of shunts such that the oxygenated blood supply to the brain is increased. Blood flow quantification enables assessment of the severity of the fetal pathology, which in turn allows for suitable&#160;in utero&#160;patient management and planning for postnatal care.
The primary challenges of applying phase contrast MRI to the human fetus include small blood vessel size, high fetal heart rate, potential MRI data corruption due to maternal respiration, unpredictable fetal movements, and lack of conventional cardiac gating methods to synchronize data acquisition. Here, we describe recent technical developments from our lab that have enabled the quantification of fetal blood flow using phase contrast MRI, including advances in accelerated imaging, motion compensation, and cardiac gating.

In general, phase MRI examinations of flow target six major fetal vessels: the descending aorta, ascending aorta, main pulmonary artery, ductus arteriosus, superior vena cava, and umbilical vein. These vessels are of interest to the clinician as they are often implicated in CHD and FGR, influencing the distribution of blood throughout the fetus9. A typical scan duration with the radial phase contrast MRI is 17 s per vessel such that the scans are short while also allowing time for enough data acqu...

Watch this Scientific Journal Video about Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation at JoVE.com

Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation

Here we present a protocol for measuring fetal blood flow rapidly with MRI and retrospectively performing motion correction and cardiac gating.

Magnetic resonance imaging (MRI) is an important tool for the clinical assessment of cardiovascular morphology and heart function. It is also the ...

human-fetal-blood-flow-quantification-with-magnetic-resonance-imaging

Research

JoVE Journal

Medicine

1.9K Views.  University of Toronto. Here we present a protocol for measuring fetal blood flow rapidly with MRI and retrospectively performing motion correction and cardiac gating.

Video: Human Fetal Blood Flow Quantification with Magnetic Resonance Imaging and Motion Compensation

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia 
(FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images 
were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial 
spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast 
gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification 
of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). 
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations 
were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, 
respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. 
Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. 
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). 
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). 
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.

A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

Isolation, Culture, and Imaging of Human Fetal Pancreatic Cell Clusters

For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning endocrine cells, as evidenced by a significant increase in circulating human C-peptide following glucose stimulation1-9. However in vitro, genesis of insulin producing cells from human fetal ICCs is low10; results reminiscent of recent experiments performed with human embryonic stem cells (hESC), a renewable source of cells that hold great promise as a potential therapeutic treatment for type 1 diabetes. Like ICCs, transplantation of partially differentiated hESC generate glucose responsive, insulin producing cells, but in vitro genesis of insulin producing cells from hESC is much less robust11-17. A complete understanding of the factors that influence the growth and differentiation of endocrine precursor cells will likely require data generated from both ICCs and hESC. While a number of protocols exist to generate insulin producing cells from hESC in vitro11-22, far fewer exist for ICCs10,23,24. Part of that discrepancy likely comes from the difficulty of working with human fetal pancreas. Towards that end, we have continued to build upon existing methods to isolate fetal islets from human pancreases with gestational ages ranging from 12 to 23 weeks, grow the cells as a monolayer or in suspension, and image for cell proliferation, pancreatic markers and human hormones including glucagon and C-peptide. ICCs generated by the protocol described below result in C-peptide release after transplantation under the kidney capsule of nude mice that are similar to C-peptide levels obtained by transplantation of fresh tissue6. Although the examples presented here focus upon the pancreatic endoderm proliferation and &#946;&#160;cell genesis, the protocol can be employed to study other aspects of pancreatic development, including exocrine, ductal, and other hormone producing cells.

A protocol to isolate, culture, and image islet cell clusters (ICCs) derived from human fetal pancreatic cells is described.&#160; The method details the steps necessary to generate ICCs from tissue, culture as monolayers or in suspension as aggregates, and image for markers of proliferation and pancreatic cell fate decisions.

For almost 30 years, scientists have demonstrated that human fetal ICCs transplanted under the kidney capsule of nude mice matured into functioning ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Cardiac Magnetic Resonance Imaging at 7 Tesla

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher magnetic field strengths and potentially provides improved signal contrast and spatial resolution. While promising results have been achieved, ultra-high field CMR is challenging due to energy deposition constraints and physical phenomena such as transmission field non-uniformities and magnetic field inhomogeneities. In addition, the magneto-hydrodynamic effect renders the synchronization of the data acquisition with the cardiac motion difficult. The challenges are currently addressed by explorations into novel magnetic resonance technology. If all impediments can be overcome, ultra-high field CMR may generate new opportunities for functional CMR, myocardial tissue characterization, microstructure imaging or metabolic imaging. Recognizing this potential, we show that multi-channel radio frequency (RF) coil technology tailored for CMR at 7 Tesla together with higher order B0 shimming and a backup signal for cardiac triggering facilitates high fidelity functional CMR. With the proposed setup, cardiac chamber quantification can be accomplished in examination times similar to those achieved at lower field strengths. To share this experience and to support the dissemination of this expertise, this work describes our setup and protocol tailored for functional CMR at 7 Tesla.

The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Quantification of Levator Ani Hiatus Enlargement by Magnetic Resonance Imaging in Males and Females with Pelvic Organ Prolapse

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while evacuating acoustic gel, using a horizontally oriented 1.5 T magnetic resonance (MR) scanner. On midsagittal images, the vertical distance of pelvic organs is measured in millimeters relative to the hymen plane (female) and to the lower border of the symphysis pubis (male), preceded by - (above) or + ( below) signs. On axial images, the levator ani area is calculated in square centimeters with a free-hand tracing method from three key images, passing through the midsymphysis (level I), tangential to the lower border of the symphysis (level II), and at the maximal anterior rectal wall bulging (level III). Areas at rest and strained are compared to find evidence of a percentage of increase. The purpose is to provide objective evidence of the maximal extent of pelvic organs descent and hiatus enlargement without the interference of foreign objects or the examiner&#39;s proximity, so as to overcome the limitations of pelvic examination and transperineal sonography (i.e., subjectivity and sex-related limitations [female only]).

Here we present a protocol to standardize the measurement of the levator ani hiatus size&#160;by magnetic resonance imaging. The purpose is to extract biomechanical inferences from image analysis by comparing resting and straining values in patients of both sexes with pelvic prolapse, using consistent anatomical bony landmarks.

Here we present a protocol to examine the levator ani hiatus in males and females with pelvic organ prolapse, during the Valsalva maneuver and while ...

Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of the fresh gas entering a lung region divided by the region&#8217;s end-expiratory volume &#8213; in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue&#8217;s longitudinal relaxation time (T1), and thus a change in tissue oxygenation can be detected as a change in T1-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T1, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T1-weighted images in a 1.5&#160;T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Specific ventilation imaging is a functional magnetic resonance imaging technique that allows for quantification of regional specific ventilation in the human lung, using inhaled oxygen as a contrast agent. Here, we present a protocol to collect and analyze specific ventilation imaging data.

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of ...