Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

BACKGROUND: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes. OBJECTIVES: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD. METHODS: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content. Superior vena cava (SVC) flow was used as a proxy for cerebral blood flow. Primary outcomes were 18-month mortality and Bayley Scales of Infant Development-III assessment. RESULTS: A total of 144 fetuses with cyanotic CHD were assessed. By 18 months, 18 patients (12.5%) died. Early mortality was associated with reduced combined ventricular output (P = 0.01), descending aortic flow (P = 0.04), and umbilical vein flow (P = 0.03). Of the surviving patients, 71 had ND outcomes assessed. Cerebral oxygen delivery was the fetal hemodynamic variable most strongly associated with cognitive, language, and motor outcomes (P < 0.05). Fetal SVC flow was also associated with cognitive, language, and motor outcomes (P < 0.01), and it remained an independent predictor of cognitive (P = 0.002) and language (P = 0.04) outcomes after adjusting for diagnosis. Diminished SVC flow also performed better than other fetal CMR and echocardiographic predictors of cognitive ND delay (receiver-operating characteristic curve area: 0.85; SE 0.05). CONCLUSIONS: Among fetuses with cyanotic CHD, diminished fetal combined ventricular output is associated with mortality, whereas cerebral blood flow and oxygen delivery are associated with early cognitive, language, and motor development at 18 months of age. These results support the inclusion of fetal CMR to help identify patients at risk of adverse ND outcomes.

An MRI approach to assess placental function in healthy humans and sheep.

KEY POINTS: Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( VO2 ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VO2 by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental VO2 by MRI was ∼4 ml min-1  kg-1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental VO2 , which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and VO2 , and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. ABSTRACT: It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( VO2 ) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ( DO2 ) and VO2 in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal DO2 and VO2 . Maternal DO2 (ml min-1  kg-1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal DO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VO2 (ml min-1  kg-1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal VO2 ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min-1  kg-1 fetus) decreased with advancing age (P = 0.008), while fetal VO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VO2 was preserved through stable umbilical flow (ml min-1  kg-1 ; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal VO2 between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'.

Normal human and sheep fetal vessel oxygen saturations by T2 magnetic resonance imaging.

KEY POINTS: Human fetal Doppler ultrasound and invasive blood gas measurements obtained by cordocentesis or at the time of delivery reveal similarities with sheep (an extensively used model for human fetal cardiovascular physiology). Oxygen saturation (SO2 ) measurements in human fetuses have been limited to the umbilical and scalp vessels, providing little information about normal regional SO2 differences in the fetus. Blood T2 MRI relaxometry presents a non-invasive measure of SO2 in the major fetal vessels. This study presents the first in vivo validation of fetal vessel T2 oximetry against the in vitro T2-SO2 relationship using catheterized sheep fetuses and compares the normal SO2 in the major vessels between the human and sheep fetal circulations. Human fetal vessel SO2 by T2 MRI confirms many similarities with the sheep fetal circulation and is able to demonstrate regional differences in SO2 ; in particular the significantly higher SO2 in the left versus right heart. ABSTRACT: Blood T2 magnetic resonance imaging (MRI) relaxometry non-invasively measures oxygen saturation (SO2 ) in major vessels but has not been validated in fetuses in vivo. We compared the blood T2-SO2 relationship in vitro (tubes) and in vivo (vessels) in sheep, and measured SO2 across the normal human and sheep fetal circulations by T2. Singleton pregnant ewes underwent surgery to implant vascular catheters. In vitro and in vivo sheep blood T2 measurements were related to corresponding SO2 measured using a blood gas analyser, as well as relating T2 and SO2 of human fetal blood in vitro. MRI oximetry was performed in the major vessels of 30 human fetuses at 36 weeks (term, 40 weeks) and 10 fetal sheep (125 days; term, 150 days). The fidelity of in vivo fetal T2 oximetry was confirmed through comparison of in vitro and in vivo sheep blood T2-SO2 relationships (P = 0.1). SO2 was similar between human and sheep fetuses, as was the fetal oxygen extraction fraction (human, 33 ± 11%; sheep, 34 ± 7%; P = 0.798). The presence of streaming in the human fetal circulation was demonstrated by the SO2 gradient between the ascending aorta (68 ± 10%) and the main pulmonary artery (49 ± 9%; P < 0.001). Human and sheep fetal vessel MRI oximetry based on T2 is a validated approach that confirms the presence of streaming of umbilical venous blood towards the heart and brain. Streaming is important in ensuring oxygen delivery to these organs and its disruption may have important implications for organ development, especially in conditions such as congenital heart disease and fetal growth restriction.

Simulation of semilunar valve function: computer-aided design, 3D printing and flow assessment with MR.

BACKGROUND: The structure of the valve leaflets and sinuses are crucial in supporting the proper function of the semilunar valve and ensuring leaflet durability. Therefore, an enhanced understanding of the structural characteristics of the semilunar valves is fundamental to the evaluation and staging of semilunar valve pathology, as well as the development of prosthetic or bioprosthetic valves. This paper illustrates the process of combining computer-aided design (CAD), 3D printing and flow assessment with 4-dimensional flow magnetic resonance imaging (MRI) to provide detailed assessment of the structural and hemodynamic characteristics of the normal semilunar valve. METHODS: Previously published geometric data on the aortic valve was used to model the 'normal' tricuspid aortic valve with a CAD software package and 3D printed. An MRI compatible flow pump with the capacity to mimic physiological flows was connected to the phantom. A peak flow rate of 100 mL/s and heart rate of 60 beats per minute were used. MRI measurements included cine imaging, 2D and 4D phase-contrast imaging to assess valve motion, flow velocity and complex flow patterns. RESULTS: Cine MRI data showed normal valve function and competency throughout the cardiac cycle in the 3D-printed phantom. Quantitative analysis of 4D Flow data showed net flow through 2D planes proximal and distal to the valve were very consistent (26.03 mL/s and 26.09 mL/s, respectively). Measurements of net flow value agreed closely with the flow waveform provided to the pump (27.74 mL/s), confirming 4D flow acquisition in relation to the pump output. Peak flow values proximal and distal to the valve were 78.4 mL/s and 63.3 mL/s, respectively. Particle traces of flow from 4D-phase contrast MRI data demonstrated flow through the valve into the ascending aorta and vortices within the aortic sinuses, which are expected during ventricular diastole. CONCLUSION: In this proof of concept study, we have demonstrated the ability to generate physiological 3D-printed aortic valve phantoms and evaluate their function with cine- and 4D Flow MRI. This technology can work synergistically with promising tissue engineering research to develop optimal aortic valve replacements, which closely reproduces the complex function of the normal aortic valve.

The utility of MRI for measuring hematocrit in fetal anemia.

BACKGROUND: Doppler ultrasound measurements of the peak systolic velocity of the middle cerebral artery can be used to noninvasively diagnose fetal anemia but are less precise following fetal blood transfusion and in late gestation. We have previously demonstrated the feasibility of estimating fetal hematocrit in vitro using magnetic resonance imaging relaxation times. Here we report the use of magnetic resonance imaging as a noninvasive tool to accurately detect fetal anemia in vivo. OBJECTIVES: This study has 2 objectives: (1) to determine the feasibility and accuracy of magnetic resonance imaging in estimating hematocrit in anemic fetuses and (2) to compare magnetic resonance imaging and middle cerebral artery Doppler in detecting moderate to severe fetal anemia. STUDY DESIGN: Fetuses undergoing fetal blood sampling or transfusion underwent magnetic resonance imaging examinations prior to and following their procedures at 1.5 Tesla (Siemens Avanto). A modified Look-Locker inversion pulse sequence and T2 preparation sequence were applied for T1 and T2 mapping of the intrahepatic umbilical vein. Estimated fetal hematocrit was calculated using a combination of T1 and T2 values and compared with conventional hematocrit obtained from fetal blood samples and middle cerebral artery Doppler measurements. RESULTS: Twenty-three fetuses were assessed during 33 magnetic resonance imaging scans. The mean absolute difference between the laboratory and magnetic resonance imaging-estimated hematocrit was 0.06 ± 0.05 with a correlation of 0.77 (P < .001) determined by a multilevel, mixed-effects model adjusting for the repeated measurements from the same participants, multiple gestation pregnancies, and the scan type (ie, before or after transfusion scan). Bland-Altman analysis revealed a systematic bias of -0.03 between the magnetic resonance imaging and fetal blood sampling measurements. Magnetic resonance imaging and middle cerebral artery Doppler had similar sensitivities of approximately 90% to detect moderate to severe anemia. However, magnetic resonance imaging had a higher specificity (93% [13/14], 95% confidence interval, 66-100%) than Doppler (71% [10/14], 95% confidence interval, 42-92%). CONCLUSION: Moderate to severe fetal anemia can be detected noninvasively by magnetic resonance imaging with high sensitivity and specificity. Our results suggest an adjunct role for magnetic resonance imaging in fetuses with suspected anemia, particularly following previous transfusion and in late gestation.

Magnetic Resonance Imaging: A New Tool to Optimize the Prediction of Fetal Anemia?

INTRODUCTION: The false-positive rate in the prediction of fetal anemia is 10-15%. We investigated if a new, noninvasive MRI method used as a supplement to ultrasound could improve the prediction. METHODS: Fetuses suspected of anemia and controls were scanned in a 1.5-tesla MRI scanner 1-4 times during pregnancy. Cases were scanned before and after intrauterine blood transfusion with a T1-mapping MRI sequence in a cross-section of the umbilical vein. RESULTS: Inclusion of 8 cases and 11 controls resulted in 10 case scans (2 cases were included twice) and 33 control scans. In controls, the T1 relaxation time was 1,005-1,391 ms; in cases with severe anemia, 1,505-1,595 ms, moderate anemia 1,503-1,525 ms, and no/mild anemia 1,245-1,410 ms. After blood transfusions, values dropped to 1,123-1,288 ms. The mean value in moderate and severe anemic cases was 275 ms higher than in controls (95% CI 210-341 ms, p < 0.0001), and after blood transfusion it was comparable to controls (3 ms, 95% CI -62 to 68 ms, p = 0.934). A 1,450-ms cut-off would have identified all cases in need of blood transfusion with no false-positive cases. CONCLUSIONS: Our findings indicate a potential for this new MRI method to improve the prediction of fetal anemia as a supplement to ultrasound.

Human umbilical cord blood relaxation times and susceptibility at 3 T.

PURPOSE: To characterize the magnetic susceptibility and relaxation times (T1 and T2 ) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen saturation (sO2 ). METHODS: Susceptibility and relaxometry measurements were performed on cord blood specimens (N = 90, derived from six caesarean deliveries) with a range of hematocrits and oxygen saturations (0.09 < Hct < 0.82, 7 < sO2 < 100%). To obtain simple, analytic relationships between MRI properties and blood properties, data were fit to established two-compartment (plasma and erythrocytes) models. RESULTS: Two-compartment models effectively described the cord blood data. The root-mean-squared deviation between the model and the data was 6.3, 10.3, and 1.3% for fits to T1 , T2 , and susceptibility measurements. Relaxometry data and estimated T1 and T2 model parameters were generally consistent with those reported in cord blood at 1.5 T and comparable to published values for adult blood. Notably, the measured value of Δχdeo , the susceptibility difference between fully oxygenated (sO2 = 100%) and deoxygenated (sO2 = 0) cord blood was approximately 20% lower than the established adult blood value (Δχdeo,cord = 2.64 ppm, Δχdeo,adult = 3.4 ppm). CONCLUSIONS: The described models and associated parameter values can be used to inform acquisition parameters, and interpret fetal/neonatal blood susceptibility measurements and relaxometry data acquired at 3 T with respect to hematocrit and sO2 . Magn Reson Med 79:3194-3206, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

New advances in fetal cardiovascular magnetic resonance imaging for quantifying the distribution of blood flow and oxygen transport: Potential applications in fetal cardiovascular disease diagnosis and therapy.

Until recently, our modern understanding of fetal circulatory physiology has been largely based on invasive measurements made in fetal sheep. However, new MRI technology developed by our group has provided equivalent information about the distribution of blood flow and oxygen transport noninvasively. The initial findings largely confirm prior estimates about the human fetal circulation extrapolated from fetal sheep data and human ultrasound data. Here we describe the hemodynamics of the normal late gestation human fetal circulation by MRI and speculate about what the advent of this technology might mean in terms of the management of fetuses affected by placental insufficiency and congenital heart disease.

Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood.

PURPOSE: We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2 ) from measurements of its T1 and T2 relaxation times. THEORY: Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO2 in terms of R1 and R2 . Resulting solutions for Hct and sO2 are the roots of cubic polynomials. METHODS: Feasibility of the method was established by comparison of Hct and sO2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T1 , T2 measurement uncertainty on precision of Hct and sO2 estimates. RESULTS: Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO2 estimates. CONCLUSION: Results demonstrate accurate quantification of Hct and sO2 from T1 and T2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med 78:2352-2359, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Relaxation properties of human umbilical cord blood at 1.5 Tesla.

PURPOSE: To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla. METHODS: Relaxometry measurements were performed on cord blood specimens (N = 88, derived from six caesarean deliveries) spanning a broad range of hematocrits (Hct = 0.19-0.76) and oxygen saturations (sO2 = 4-100%), to characterize the dependence of T1 and T2 on these blood properties. Adult blood data (N = 31 specimens, derived from two volunteers) were similarly studied to validate our experimental methods by comparison with existing literature. Using biophysical models previously developed for adult blood, new model parameters were estimated, which relate Hct and sO2 to the observed cord blood relaxation times. RESULTS: Fitted biophysical models explained more than 90% of the variation in T1 and T2 . In general, T2 relaxation times of cord blood were longer (by up to 35%) than those of adult blood, whereas T1 relaxation times were slightly shorter (by up to 10%). CONCLUSIONS: The models and fitted parameters presented here can be used for calibration of future MRI investigations of fetal and neonatal blood physiology. This study is an important step in facilitating accurate, noninvasive assessments of fetal blood oxygen content, a valuable diagnostic parameter in the identification and treatment of fetal hypoxia. Magn Reson Med 77:1678-1690, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

The hemodynamics of late-onset intrauterine growth restriction by MRI.

BACKGROUND: Late-onset intrauterine growth restriction (IUGR) results from a failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late-gestation fetus. Limitations in current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a noninvasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods. OBJECTIVE: The objective of the study was to use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset IUGR fetuses. STUDY DESIGN: This was a prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebroplacental ratio were acquired using ultrasound. A score of ≥ 2 of the 4 following parameters defined IUGR: (1) birthweight the third centile or less or 20% or greater drop in the centile in estimated fetal weight; (2) lowest cerebroplacental ratio after 30 weeks less than the fifth centile; (3) ponderal index < 2.2; and (4) placental histology meets predefined criteria for placental underperfusion. Measurements were compared between the 2 groups (Student t test) and correlations between parameters were analyzed (Pearson's correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver-operating characteristic curves. RESULTS: We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks' gestation. IUGR fetuses had lower umbilical vein (P = .004) and pulmonary blood flow (P = .01) and higher superior vena caval flow (P < .0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normal fetuses (P < .0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index, and cerebroplacental ratio were all significantly lower in IUGR fetuses, whereas there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow and inversely with oxygen delivery, oxygen consumption, umbilical vein T2, and cerebroplacental ratio. Receiver-operating characteristic curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow area under the curve of 0.94 (95% confidence interval, 0.87-1.00) vs a cerebroplacental ratio area under the curve of 0.80 (95% confidence interval, 0.64-0.97). CONCLUSION: MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, whereas reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.

Magnetic resonance microscopy of human and porcine neurons and cellular processes.

With its unparalleled ability to safely generate high-contrast images of soft tissues, magnetic resonance imaging (MRI) has remained at the forefront of diagnostic clinical medicine. Unfortunately due to resolution limitations, clinical scans are most useful for detecting macroscopic structural changes associated with a small number of pathologies. Moreover, due to a longstanding inability to directly observe magnetic resonance (MR) signal behavior at the cellular level, such information is poorly characterized and generally must be inferred. With the advent of the MR microscope in 1986 came the ability to measure MR signal properties of theretofore unobservable tissue structures. Recently, further improvements in hardware technology have made possible the ability to visualize mammalian cellular structure. In the current study, we expand upon previous work by imaging the neuronal cell bodies and processes of human and porcine α-motor neurons. Complimentary imaging studies are conducted in pig tissue in order to demonstrate qualitative similarities to human samples. Also, apparent diffusion coefficient (ADC) maps were generated inside porcine α-motor neuron cell bodies and portions of their largest processes (mean=1.7 ± 0.5 µm²/ms based on 53 pixels) as well as in areas containing a mixture of extracellular space, microvasculature, and neuropil (0.59 ± 0.37 µm²/ms based on 33 pixels). Three-dimensional reconstruction of MR images containing α-motor neurons shows the spatial arrangement of neuronal projections between adjacent cells. Such advancements in imaging portend the ability to construct accurate models of MR signal behavior based on direct observation and measurement of the components which comprise functional tissues. These tools would not only be useful for improving our interpretation of macroscopic MRI performed in the clinic, but they could potentially be used to develop new methods of differential diagnosis to aid in the early detection of a multitude of neuropathologies.

An efficient interlaced multi-shell sampling scheme for reconstruction of diffusion propagators.

In this paper, we propose an interlaced multi-shell sampling scheme for the reconstruction of the diffusion propagator from diffusion weighted magnetic resonance imaging (DW-MRI). In standard multi-shell sampling schemes, sample points are uniformly distributed on several spherical shells in q-space. The distribution of sample points is the same for all shells, and is determined by the vertices of a selected polyhedron. We propose a more efficient interlaced scheme where sample points are different on alternating shells and are determined by the vertices of a pair of dual polyhedra. Since it samples more directions than the standard scheme, this method offers increased angular discrimination. Another contribution of this work is the application of optimal sampling lattices to q-space data acquisition and the proposal of a model-free reconstruction algorithm, which uses the lattice dependent sinc interpolation function. It is shown that under this reconstruction framework, the body centered cubic (BCC) lattice provides increased accuracy. The sampling scheme and the reconstruction algorithms were evaluated on simulated data as well as rat brain data collected on a 600 MHz (14.1T) Bruker imaging spectrometer.

BOX SPLINE BASED 3D TOMOGRAPHIC RECONSTRUCTION OF DIFFUSION PROPAGATORS FROM MRI DATA.

This paper introduces a tomographic approach for reconstruction of diffusion propagators, P( r ), in a box spline framework. Box splines are chosen as basis functions for high-order approximation of P( r ) from the diffusion signal. Box splines are a generalization of B-splines to multivariate setting that are particularly useful in the context of tomographic reconstruction. The X-Ray or Radon transform of a (tensor-product B-spline or a non-separable) box spline is a box spline - the space of box splines is closed under the Radon transform.We present synthetic and real multi-shell diffusion-weighted MR data experiments that demonstrate the increased accuracy of P( r ) reconstruction as the order of basis functions is increased.

Comparative SNR for high-throughput mouse embryo MR microscopy.

MR microscopy is being explored as a useful imaging tool to phenotype mouse embryos due to its volume coverage with three-dimensional isotropic resolution. However, the main limitation for mouse embryo MR microscopy is the signal-to-noise ratio. Large numbers of embryos are needed for phenotypic screening, making high throughput essential. Two high-throughput imaging approaches, multi-embryo shared-coil (shared) and multi-embryo individual-coil (individual), have been developed for phenotyping mouse embryos. This study quantitatively compares the signal-to-noise ratio at equivalent times between these two established methods by compensating for differences that result from field strength. While the individual method provides 3.3 times as much signal-to-noise ratio as the shared method at equivalent conditions, it is more difficult and expensive to implement. Furthermore, the number of embryos that can be imaged concurrently is limited by the number of receiver channels. The objective of this study is to provide measured comparative data to guide choices for high-throughput mouse embryo MR microscopy and other similar applications.

Dimensions of the human sclera: Thickness measurement and regional changes with axial length.

Scleral thickness, especially near the region of the optic nerve head (ONH), is a potential factor of interest in the development of glaucomatous optic neuropathy. Our goal was to characterize the scleral thickness distribution and other geometric features of human eyes. Eleven enucleated human globes (7 normal and 4 ostensibly glaucomatous) were imaged using high-field microMRI, providing 80 microm isotropic resolution over the whole eye. The MRI scans were segmented to produce 3-D corneoscleral shells. Each shell was divided into 15 slices along the anterior-posterior axis of the eye, and each slice was further subdivided into the anatomical quadrants. Average thickness was measured in each region, producing 60 thickness measurements per eye. Hierarchical clustering was used to identify trends in the thickness distribution, and scleral geometric features were correlated with globe axial length. Thickness over the whole sclera was 670 +/- 80 microm (mean +/- SD; range: 564 microm-832 microm) over the 11 eyes. Maximum thickness occurred at the posterior pole of the eye, with mean thickness of 996 +/- 181 microm. Thickness decreased to a minimum at the equator, where a mean thickness of 491 +/- 91 microm was measured. Eyes with a reported history of glaucoma were found to have longer axial length, smaller ONH canal dimensions and thinner posterior sclera. Several geometrical parameters of the eye, including posterior scleral thickness, axial length, and ONH canal diameter, appear linked. Significant intra-individual and inter-individual variation in scleral thickness was evident. This may be indicative of inter-individual differences in ocular biomechanics.

Modeling pulsed magnetization transfer.

Modeling the effects of clinical magnetization transfer (MT) scans, which generate contrast using short, shaped radiofrequency (RF) pulses (pulsed MT), is complex and time-consuming. As a result, several studies have proposed approximate methods for a simplified analysis of the experimental data. However, potential differences in the MT parameters estimated by each method may complicate the comparison of reported results. In this study we evaluated three approximate methods currently used in quantitative MT (qMT) studies. In the first part of the investigation, an MT modeling technique that makes minimal approximations, other than the use of a two-pool tissue representation, was developed and validated. Subsequently, this technique served as a standard against which to evaluate the other, more approximate models. Each model was used to fit experimental data from samples of wild-type (WT) and shiverer mouse spinal cord, as well as simulated data generated by our minimal approximation modeling technique. The results of this study demonstrate that the approximations used in pulsed MT modeling are quite robust. In particular, it was shown that the semisolid pool fraction, M(0)(B), which is known to correlate strongly with myelin content, and the transverse relaxation time of macromolecular protons, T(2)(B), could be evaluated with reasonable accuracy regardless of the model used.