Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.

BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.

AMH predicts miscarriage in non-PCOS but not in PCOS related infertility ART cycles.

BACKGROUND: To study whether AMH levels were associated with miscarriage rates in index ART cycles undergoing fresh autologous transfers in PCOS and non-PCOS related infertility. METHODS: In the SART CORS database 66,793 index cycles underwent fresh autologous embryo transfers with AMH values reported within the last 1-year between 2014 and 2016. Cycles that resulted in ectopic or heterotopic pregnancies, or were performed for embryo/oocyte banking were excluded. Data were analyzed using Graphpad Prism-9. Odds ratios (OR) were calculated with 95% confidence intervals (CI) along with multivariate regression analysis adjusting for age, body mass index (BMI), and number of embryos transferred. Miscarriage rates were calculated as miscarriage per clinical pregnancies. RESULTS: Of the total 66,793 cycles, the mean AMH was 3.2 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 1.1, CI 0.9-1.4, p = 0.3). Of the 8,490 PCOS patients, the mean AMH was 6.1 ng/ml and were not associated with increased miscarriage rates for AMH < 1 ng/ml (OR 0.8, CI 0.5-1.1, p = 0.2). Of the 58,303 non-PCOS patients, the mean AMH was 2.8 ng/ml and there was a significant difference in miscarriage rates for AMH < 1 ng/ml (OR 1.2, CI 1.1-1.3, p < 0.01). All findings were independent of age, BMI and number of embryos transferred. This statistical significance did not persist at higher thresholds of AMH. The overall miscarriage rate for all cycles, and cycles with and without PCOS were each 16%. DISCUSSION: The clinical utility of AMH continues to increase as more studies investigate its predictive abilities regarding reproductive outcomes. This study adds clarity to the mixed findings of prior studies that have examined the relationship between AMH and miscarriage in ART cycles. AMH values of the PCOS population are higher than the non-PCOS. The elevated AMH associated with PCOS decreases its utility in predicting miscarriages in IVF cycles as it may be representing the number of developing follicles rather than oocyte quality in the PCOS patient population. The elevated AMH associated with PCOS may have skewed the data; removing this sub-population may have unmasked significance within the non-PCOS associated infertility. CONCLUSIONS: AMH < 1 ng/mL is an independent predictor of increased miscarriage rate in patients with non-PCOS infertility.

Inhaled gene therapy of preclinical muco-obstructive lung diseases by nanoparticles capable of breaching the airway mucus barrier.

INTRODUCTION: Inhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases. METHODS: We investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, Scnn1b-Tg) and in air-liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis. A plasmid designed to silence epithelial sodium channel (ENaC) hyperactivity, which causes airway surface dehydration and mucus stasis, was intratracheally administered via DNA-MPP to evaluate therapeutic effects in vivo with or without pretreatment with hypertonic saline, a clinically used mucus-rehydrating agent. RESULTS: DNA-MPP exhibited marked greater reporter transgene expression compared with a mucus-impermeable formulation in in vivo and in vitro models of muco-obstructive lung diseases. DNA-MPP carrying ENaC-silencing plasmids provided efficient downregulation of ENaC and reduction of mucus burden in the lungs of Scnn1b-Tg mice, and synergistic impacts on both gene transfer efficacy and therapeutic effects were achieved when DNA-MPP was adjuvanted with hypertonic saline. DISCUSSION: DNA-MPP constitutes one of the rare gene delivery systems providing therapeutically meaningful gene transfer efficacy in highly relevant in vivo and in vitro models of muco-obstructive lung diseases due to its unique ability to efficiently penetrate airway mucus.

Self-gated 4D multiphase, steady-state imaging with contrast enhancement (MUSIC) using rotating cartesian K-space (ROCK): Validation in children with congenital heart disease.

PURPOSE: To develop and validate a cardiac-respiratory self-gating strategy for the recently proposed multiphase steady-state imaging with contrast enhancement (MUSIC) technique. METHODS: The proposed SG strategy uses the ROtating Cartesian K-space (ROCK) sampling, which allows for retrospective k-space binning based on motion surrogates derived from k-space center line. The k-space bins are reconstructed using a compressed sensing algorithm. Ten pediatric patients underwent cardiac MRI for clinical reasons. The original MUSIC and 2D-CINE images were acquired as a part of the clinical protocol, followed by the ROCK-MUSIC acquisition, all under steady-state intravascular distribution of ferumoxytol. Subjective scores and image sharpness were used to compare the images of ROCK-MUSIC and original MUSIC. RESULTS: All scans were completed successfully without complications. The ROCK-MUSIC acquisition took 5 ± 1 min, compared to 8 ± 2 min for the original MUSIC. Image scores of ROCK-MUSIC were significantly better than original MUSIC at the ventricular outflow tracts (3.9 ± 0.3 vs. 3.3 ± 0.6, P < 0.05). There was a strong trend toward superior image scores for ROCK-MUSIC in the other anatomic locations. CONCLUSION: ROCK-MUSIC provided images of equal or superior image quality compared to original MUSIC, and this was achievable with 40% savings in scan time and without the need for physiologic signal. Magn Reson Med 78:472-483, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous acquisition of T1ρ and T2 quantification in knee cartilage: repeatability and diurnal variation.

PURPOSE: To develop a robust sequence that combines T1ρ and T2 quantifications and to examine the in vivo repeatability and diurnal variation of T1ρ and T2 quantifications in knee cartilage. MATERIALS AND METHODS: Six healthy volunteers were scanned in the morning and afternoon on 2 days using a combined T1ρ and T2 quantification sequence developed in this study. Repeatability of T1ρ and T2 quantification was estimated using root-mean-square coefficients-of-variation (RMS-CV). T1ρ and T2 values from morning scans were compared to those from afternoon scans using paired t-tests. RESULTS: The overall RMS-CV of in vivo T1ρ and T2 quantification was 5.3% and 5.2%, respectively. The RMS-CV of am scans was 4.2% and 5.0% while the RMS-CV of pm scans was 6.0% and 6.3% for T1ρ and T2 , respectively. No significant difference was found between T1ρ or T2 values in the morning and in the afternoon. CONCLUSION: A sequence that combines T1ρ and T2 quantification with scan time less than 10 minutes and is robust to B0 and B1 inhomogeneity was developed with excellent repeatability. For a cohort with low-level daily activity, although no significant diurnal variation of cartilage MR relaxation times was observed, the afternoon scans had inferior repeatability compared to morning scans.

Oocyte Cryopreservation for Medical and Planned Indications: A Practical Guide and Overview.

Oocyte cryopreservation (OC) is the process in which ovarian follicles are stimulated, the follicular fluid is retrieved, and mature oocytes are isolated and vitrified. Since the first successful pregnancy utilizing previously cryopreserved oocytes in 1986, OC has become increasingly utilized as an option for future biologic children in patients facing gonadotoxic therapies, such as for the treatment of cancer. Planned OC, also termed elective OC, is growing in popularity as a means to circumvent age-related fertility decline. In this narrative review, we describe both medically indicated and planned OC, focusing on the physiology of ovarian follicular loss, OC technique and risks, timing of when OC should be performed, associated financial considerations, and outcomes.

The relationship between dietary inflammatory potential and cancer outcomes among cancer survivors: A systematic review and meta-analysis of cohort studies.

Cancer remains the second leading cause of death globally. Chronic inflammatory environments promote the growth of tumors, and the intake of certain food items can increase systemic inflammation. This study examined the relationship between the inflammatory potential of diet, measured by the Dietary Inflammatory Index (DII), and recurrence, all-cause, and cancer-specific mortality among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched in April 2022. Two independent reviewers screened all searches. Of the 1,443 studies, 13 studies involving 14,920 cancer survivors passed all the screening stages. Three studies reported cancer recurrence, 12 reported all-cause mortality, and six reported cancer-specific mortality. Seven studies calculated DII from pre-diagnosis diets, five from post-diagnosis diets, and one from both pre-and post-diagnosis diets. A random-effects model meta-analysis showed that high DII was not associated with an increased risk of recurrence (HR = 1.09, 95 % CI = 0.77, 1.54, n = 4) and all-cause (HR = 1.08, 95 % CI = 0.99, 1.19, n = 14) and cancer-specific mortality (H = 1.07, 95 % CI = 0.92, 1.25, n = 6). Analysis by the timing of dietary assessment showed that only post-diagnosis DII was associated with an increased risk of all-cause mortality (HR = 1.34, 95 % CI = 1.05, 1.72, n = 6) by 34 %; however, cancer type did not modify these associations. The quality of the study assessed using the Newcastle Ottawa Scale indicated all but one studies were good. The risk of all-cause mortality among cancer survivors could be reduced by consuming more anti-inflammatory diets after cancer diagnosis.

Healthy Eating and Mortality among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

This systematic review examined the effect of diet quality, defined as adherence to healthy dietary recommendations, on all-cause and breast cancer-specific mortality. Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by May 2021. We used a random-effects model meta-analysis in two different approaches to estimate pooled hazard ratio (HR) and 95% confidence interval (CI) for highest and lowest categories of diet quality: (1) each dietary quality index as the unit of analysis and (2) cohort as the unit of analysis. Heterogeneity was examined using Cochran's Q test and inconsistency I2 statistics. The risk of bias was assessed by the Newcastle-Ottawa Scale for cohort studies, and the quality of evidence was investigated by the GRADE tool. The analysis included 11 publications from eight cohorts, including data from 27,346 survivors and seven dietary indices. Both approaches yielded a similar effect size, but cohort-based analysis had a wider CI. Pre-diagnosis diet quality was not associated with both outcomes. However, better post-diagnosis diet quality significantly reduced all-cause mortality by 21% (HR = 0.79, 95% CI = 0.70, 0.89, I2 = 16.83%, n = 7) and marginally reduced breast cancer-specific mortality by 15% (HR = 0.85, 95% CI = 0.62, 1.18, I2 = 57.4%, n = 7). Subgroup analysis showed that adhering to the Diet Approaches to Stop Hypertension and Chinese Food Pagoda guidelines could reduce breast cancer-specific mortality. Such reduction could be larger for older people, physically fit individuals, and women with estrogen receptor-positive, progesterone receptor-negative, or human epidermal growth factor receptor 2-positive tumors. The risk of bias in the selected studies was low, and the quality of evidence for the identified associations was low or very low due to imprecision of effect estimation, inconsistent results, and publication bias. More research is needed to precisely estimate the effect of diet quality on mortality. Healthcare providers can encourage breast cancer survivors to comply with healthy dietary recommendations to improve overall health. (Funding: University of Central Florida Office of Undergraduate Research, Registration: PROSPERO-CRD42021260135).

Radiofrequency pulses for simultaneous short T2 excitation and long T2 suppression.

Magnetic resonance imaging of short T(2) musculoskeletal tissues such as ligaments, tendon, and cortical bone often requires specialized pulse sequences to detect sufficiently high levels of signal, as well as additional techniques to suppress unwanted long T(2) signals. We describe a specialized radiofrequency technique for imaging short T(2) tissues based on applying hard 180° radiofrequency excitation pulses to achieve simultaneous short T(2) tissue excitation and long T(2) tissue signal suppression for three-dimensional ultrashort echo time applications. A criterion for the pulse duration of the 180° radiofrequency pulses is derived that allows simultaneous water and fat suppression. This opens up possibilities for direct imaging of short T(2) tissues, without the need for additional suppression techniques. Bloch simulations and experimental studies on short T(2) phantoms and specimen were used to test the sequence performance.

Comparison of T1rho measurements in agarose phantoms and human patellar cartilage using 2D multislice spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot techniques at 3 T.

OBJECTIVE: The purpose of this article is to compare in vitro T1rho measurements in agarose phantoms and articular cartilage specimens using 2D multislice spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot MRI sequences. MATERIALS AND METHODS: Six phantoms (agarose concentration, 2%, 3%, and 4%; n = 2 each) and 10 axially sliced patellar specimens from five cadaveric donors were scanned at 3 T. T1rho-weighted images were acquired using 2D spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot sequences. Regions of interest were analyzed to measure T1rho values centrally within phantoms, to evaluate effects of pulse sequence and agarose concentration. In patellar specimens, regions of interest were analyzed to measure T1rho values with respect to anatomic location (the medial and lateral facets and the median ridge in deep and superficial halves of the cartilage) as well as location that exhibited magic angle effect in proton density-weighted images, to evaluate the effects of pulse sequence, anatomic location, and magic angle. RESULTS: In phantoms, T1rho values were similar (p = 0.9) between sequences but decreased significantly (p < 0.001), from ∼55 to ∼29 milliseconds, as agarose concentration increased from 2% to 4%. In cartilage specimens, T1rho values were also similar between sequences (p = 0.3) but were significantly higher (p < 0.001) in the superficial layer (95-120 milliseconds) compared with the deep layer (45-75 milliseconds). CONCLUSION: T1rho measurements of human patellar cartilage specimens and agarose phantoms using 2D spiral and 3D magnetization prepared partitioned k-space spoiled gradient-echo snapshot sequences gave similar values. Lower T1rho values for phantoms with higher agarose concentrations and proteoglycan concentrations that are higher in deeper layers of cartilage than in superficial layers suggest that our method is sensitive to concentration of macromolecules in biologic tissues.

Prospective motion correction improves diagnostic utility of pediatric MRI scans.

A new technique for prospectively correcting head motion (called PROMO) during acquisition of high-resolution MRI scans has been developed to reduce motion artifacts. To evaluate the efficacy of PROMO, four T1-weighted image volumes (two with PROMO enabled, two uncorrected) were acquired for each of nine children. A radiologist, blind to whether PROMO was used, rated image quality and artifacts on all sagittal slices of every volume. These ratings were significantly better in scans collected with PROMO relative to those collected without PROMO (Mann-Whitney U test, P < 0.0001). The use of PROMO, especially in motion-prone patients, should improve the accuracy of measurements made for clinical care and research, and potentially reduce the need for sedation in children.

Prevalence of cerebral small vessel disease in a Fabry disease cohort.

OBJECTIVE: To characterize the prevalence of brain ischemia and cerebral small vessel disease in a cohort of patients with Fabry disease (FD) seen at an academic medical center. BACKGROUND: FD is an inherited X-linked lysosomal storage disorder with central nervous system involvement. Limited data are available in the literature on the cerebrovascular neuroimaging findings in FD, and the reported prevalence of stroke symptoms and cerebral small vessel disease has varied widely. DESIGN/METHODS: Brain MRI was performed in 21 patients with FD followed at University of California Irvine Medical Center. Stroke symptoms were assessed and quantification of cerebral microvascular disease was performed using small vessel disease (SVD) score. Lacunes and deep white matter hyperintensities were scored on a four-point scale of 0 (absent) and 1-3 to account for increasing severity; microbleeds were scored 0 (absent) or 1 (present). The total SVD score is the sum of the three components and ranges from 0 to 7. RESULTS: Nearly 43% (9/21) of our FD cohort (aged 32-81 years, mean = 50) had a SVD score of one or higher, all of whom were aged 50 or more years. The most common MRI-defined SVD was white matter hyperintensities (9/9, 100%), followed by microbleeds (6/9, 66%), and lacunes (3/9, 33%). The three patients with previous strokes had some of the highest SVD scores reported in the cohort (scores 3-5). CONCLUSIONS: In this cohort, the prevalence of SVD (43%) was three times higher than prevalence of stroke symptoms. SVD score was highest in the those who had experienced a stroke. These findings emphasize the importance of routine MRI screening of patients with FD in order to identify and treat high risk patients.

Prospective motion correction of high-resolution magnetic resonance imaging data in children.

Motion artifacts pose significant problems for the acquisition and analysis of high-resolution magnetic resonance imaging data. These artifacts can be particularly severe when studying pediatric populations, where greater patient movement reduces the ability to clearly view and reliably measure anatomy. In this study, we tested the effectiveness of a new prospective motion correction technique, called PROMO, as applied to making neuroanatomical measures in typically developing school-age children. This method attempts to address the problem of motion at its source by keeping the measurement coordinate system fixed with respect to the subject throughout image acquisition. The technique also performs automatic rescanning of images that were acquired during intervals of particularly severe motion. Unlike many previous techniques, this approach adjusts for both in-plane and through-plane movement, greatly reducing image artifacts without the need for additional equipment. Results show that the use of PROMO notably enhances subjective image quality, reduces errors in Freesurfer cortical surface reconstructions, and significantly improves the subcortical volumetric segmentation of brain structures. Further applications of PROMO for clinical and cognitive neuroscience are discussed.

Optimization of RF excitation to maximize signal and T2 contrast of tissues with rapid transverse relaxation.

Ultrashort echo time MRI requires specialized pulse sequences to overcome the short T(2) of the MR signal encountered in tissues such as ligaments, tendon, or cortical bone. Theoretical work is presented, supported by simulations and experimental data on optimizing the radiofrequency excitation to maximize signal-to-noise ratio and contrast-to-noise ratio. The theoretical calculations and simulations are based on the classic Bloch equations and lead to a closed form expression for the optimal radiofrequency pulse parameters to maximize the MR signal in the presence of rapid T(2) decay. In the steady state, the spoiled gradient recalled echo signal amplitude in response to the radiofrequency excitation pulses is not maximized by the classic Ernst angle but by a more general criterion we call "generalized Ernst angle." Finally, it is shown that T(2) contrast is maximized by flipping the magnetization at the Ernst angle with a radiofrequency pulse duration proportional to the targeted T(2). Experimental studies on short T(2) phantoms confirm these optimization criteria for both signal-to-noise ratio and contrast-to-noise ratio.

Ultrashort TE T1rho (UTE T1rho) imaging of the Achilles tendon and meniscus.

In this study, we report the use of a novel ultrashort echo time T(1)rhoT(1) sequence that combines a spin-lock preparation pulse with a two-dimensional ultrashort echo time sequence of a nominal echo time 8 microsec. The ultrashort echo time-T(1)rho sequence was employed to quantify T(1)rho in short T(2) tissues including the Achilles tendon and the meniscus. T(1)rho dispersion was investigated by varying the spin-lock field strength. Preliminary results on six cadaveric ankle specimens and five healthy volunteers show that the ultrashort echo time-T(1)rho sequence provides high signal and contrast for both the Achilles tendon and the meniscus. The mean T(1)rho of the Achilles tendon ranged from 3.06 +/- 0.51 msec for healthy volunteers to 5.22 +/- 0.58 msec for cadaveric specimens. T(1)rho increased to 8.99 +/- 0.24 msec in one specimen with tendon degeneration. A mean T(1)rho of 7.98 +/- 1.43 msec was observed in the meniscus of the healthy volunteers. There was significant T(1)rho dispersion in both the Achilles tendon and the meniscus. Mean T(1)rho increased from 2.06 +/- 0.23 to 7.85 +/- 0.74 msec in normal Achilles tendon and from 7.08 +/- 0.64 to 13.42 +/- 0.93 msec in normal meniscus when the spin-lock field was increased from 250 to 1,000 Hz.

PROMO: Real-time prospective motion correction in MRI using image-based tracking.

Artifacts caused by patient motion during scanning remain a serious problem in most MRI applications. The prospective motion correction technique attempts to address this problem at its source by keeping the measurement coordinate system fixed with respect to the patient throughout the entire scan process. In this study, a new image-based approach for prospective motion correction is described, which utilizes three orthogonal two-dimensional spiral navigator acquisitions, along with a flexible image-based tracking method based on the extended Kalman filter algorithm for online motion measurement. The spiral navigator/extended Kalman filter framework offers the advantages of image-domain tracking within patient-specific regions-of-interest and reduced sensitivity to off-resonance-induced corruption of rigid-body motion estimates. The performance of the method was tested using offline computer simulations and online in vivo head motion experiments. In vivo validation results covering a broad range of staged head motions indicate a steady-state error of less than 10% of the motion magnitude, even for large compound motions that included rotations over 15 deg. A preliminary in vivo application in three-dimensional inversion recovery spoiled gradient echo (IR-SPGR) and three-dimensional fast spin echo (FSE) sequences demonstrates the effectiveness of the spiral navigator/extended Kalman filter framework for correcting three-dimensional rigid-body head motion artifacts prospectively in high-resolution three-dimensional MRI scans.

Ankle: isotropic MR imaging with 3D-FSE-cube--initial experience in healthy volunteers.

The purpose of this prospective study was to compare a new isotropic three-dimensional (3D) fast spin-echo (FSE) pulse sequence with parallel imaging and extended echo train acquisition (3D-FSE-Cube) with a conventional two-dimensional (2D) FSE sequence for magnetic resonance (MR) imaging of the ankle. After institutional review board approval and informed consent were obtained and in accordance with HIPAA privacy guidelines, MR imaging was performed in the ankles of 10 healthy volunteers (four men, six women; age range, 25-41 years). Imaging with the 3D-FSE-Cube sequence was performed at 3.0 T by using both one-dimensional- and 2D-accelerated autocalibrated parallel imaging to decrease imaging time. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) with 3D-FSE-Cube were compared with those of the standard 2D FSE sequence. Cartilage, muscle, and fluid SNRs were significantly higher with the 3D-FSE-Cube sequence (P < .01 for all). Fluid-cartilage CNR was similar for both techniques. The two sequences were also compared for overall image quality, blurring, and artifacts. No significant difference for overall image quality and artifacts was demonstrated between the 2D FSE and 3D-FSE-Cube sequences, although the section thickness in 3D-FSE-Cube imaging was much thinner (0.6 mm). However, blurring was significantly greater on the 3D-FSE-Cube images (P < .04). The 3D-FSE-Cube sequence with isotropic resolution is a promising new MR imaging sequence for viewing complex joint anatomy.

DWI of the spinal cord with reduced FOV single-shot EPI.

Single-shot echo-planar imaging (ss-EPI) has not been used widely for diffusion-weighted imaging (DWI) of the spinal cord, because of the magnetic field inhomogeneities around the spine, the small cross-sectional size of the spinal cord, and the increased motion in that area due to breathing, swallowing, and cerebrospinal fluid (CSF) pulsation. These result in artifacts with the usually long readout duration of the ss-EPI method. Reduced field-of-view (FOV) methods decrease the required readout duration for ss-EPI, thereby enabling its practical application to imaging of the spine. In this work, a reduced FOV single-shot diffusion-weighted echo-planar imaging (ss-DWEPI) method is proposed, in which a 2D spatially selective echo-planar RF excitation pulse and a 180 degrees refocusing pulse reduce the FOV in the phase-encode (PE) direction, while suppressing the signal from fat simultaneously. With this method, multi slice images with higher in-plane resolutions (0.94 x 0.94 mm(2) for sagittal and 0.62 x 0.62 mm(2) for axial images) are achieved at 1.5 T, without the need for a longer readout.

Development and initial evaluation of 7-T q-ball imaging of the human brain.

Diffusion tensor imaging (DTI) noninvasively depicts white matter connectivity in regions where the Gaussian model of diffusion is valid but yields inaccurate results in those where diffusion has a more complex distribution, such as fiber crossings. q-ball imaging (QBI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion with larger numbers of diffusion-encoding directional measurements at higher diffusion-weighting factors (b values). However, the former technique results in longer acquisition times and the latter technique results in a lower signal-to-noise ratio (SNR). In this project, we developed specialized 7-T acquisition methods utilizing novel radiofrequency pulses, eight-channel parallel imaging EPI and high-order shimming with a phase-sensitive multichannel B0 field map reconstruction. These methods were applied in initial healthy adult volunteer studies, which demonstrated the feasibility of performing 7-T QBI. Preliminary comparisons of 3 T with 7 T within supratentorial crossing white matter tracts documented a 79.5% SNR increase for b=3000 s/mm2 (P=.0001) and a 38.6% SNR increase for b=6000 s/mm2 (P=.015). With spherical harmonic reconstruction of the q-ball orientation distribution function at b=3000 s/mm2, 7-T QBI allowed for accurate visualization of crossing fiber tracts with fewer diffusion-encoding acquisitions as compared with 3-T QBI. The improvement of 7-T QBI at b factors as high as 6000 s/mm2 resulted in better angular resolution as compared with 3-T QBI for depicting fibers crossing at shallow angles. Although the increased susceptibility effects at 7 T caused problematic distortions near brain-air interfaces at the skull base and posterior fossa, these initial 7-T QBI studies demonstrated excellent quality in much of the supratentorial brain, with significant improvements as compared with 3-T acquisitions in the same individuals.

Isotropic MRI of the knee with 3D fast spin-echo extended echo-train acquisition (XETA): initial experience.

OBJECTIVE: The purpose of our study was to prospectively compare a recently developed method of isotropic 3D fast spin-echo (FSE) with extended echo-train acquisition (XETA) with 2D FSE and 2D fast recovery FSE (FRFSE) for MRI of the knee. SUBJECTS AND METHODS: Institutional review board approval, Health Insurance Portability and Accounting Act (HIPAA) compliance, and informed consent were obtained. We studied 10 healthy volunteers and one volunteer with knee pain using 3D FSE XETA, 2D FSE, and 2D FRFSE. Images were obtained both with and without fat suppression. Cartilage and muscle signal-to-noise ratio (SNR) and cartilage-fluid contrast-to-noise ratio (CNR) were compared using a Student's t test. We also compared reformations of 3D FSE XETA with 2D FSE images directly acquired in the axial plane. RESULTS: Cartilage SNR was higher with 3D FSE XETA (56.8 +/- 9 [SD]) compared with the 2D FSE (45.8 +/- 8, p < 0.01) and 2D FRFSE (32.5 +/- 5.3, p < 0.01). Muscle SNR was significantly higher with 3D FSE XETA (52.1 +/- 4.3) than 2D FSE (45.2 +/- 9, p < 0.01) and 2D FRFSE (23.6 +/- 6.2, p < 0.01). Fluid SNR was significantly higher for 2D FSE (144.9 +/- 33) than 3D FSE XETA (104.7 +/- 18, p < 0.01). Compared with 2D FSE and 2D FRFSE, 3D FSE XETA had lower cartilage-fluid CNR due to higher cartilage SNR (p < 0.01). Three-dimensional FSE XETA acquired volumetric data sets with isotropic resolution. Reformatted images in the axial plane were similar to axial 2D FSE acquisitions but with thinner slices. CONCLUSION: Three-dimensional FSE XETA acquires high-resolution (approximately 0.7 mm) isotropic data with intermediate and T2-weighting that may be reformatted in arbitrary planes. Three-dimensional FSE XETA is a promising technique for MRI of the knee.