Ultrasound and magnetic resonance imaging-based investigation of the role of perfusion and oxygen availability in menstrual pain.

BACKGROUND: The mechanisms responsible for menstrual pain are poorly understood. However, dynamic, noninvasive pelvic imaging of menstrual pain sufferers could aid in identifying therapeutic targets and testing novel treatments. OBJECTIVE: To study the mechanisms responsible for menstrual pain, we analyzed ultrasonographic and complementary functional magnetic resonance imaging parameters in dysmenorrhea sufferers and pain-free controls under multiple conditions. STUDY DESIGN: We performed functional magnetic resonance imaging on participants with and those without dysmenorrhea during menses and outside menses. To clarify whether regional changes in oxygen availability and perfusion occur, functional magnetic resonance imaging R2∗ measurements of the endometrium and myometrium were obtained. R2∗ measurements are calculated nuclear magnetic resonance relaxation rates sensitive to the paramagnetic properties of oxygenated and deoxygenated hemoglobin. We also compared parameters before and after an analgesic dose of naproxen sodium. In addition, we performed similar measurements with Doppler ultrasonography to identify if changes in uterine arterial velocity occurred during menstrual cramping in real time. Mixed model statistics were performed to account for within-subject effects across conditions. Corrections for multiple comparisons were made with a false discovery rate adjustment. RESULTS: During menstruation, a notable increase in R2∗ values, indicative of tissue ischemia, was observed in both the myometrium (beta ± standard error of the mean, 15.74±2.29 s-1; P=.001; q=.002) and the endometrium (26.37±9.33 s-1; P=.005; q=.008) of participants who experienced dysmenorrhea. A similar increase was noted in the myometrium (28.89±2.85 s-1; P=.001; q=.002) and endometrium (75.50±2.57 s-1; P=.001; q=.003) of pain-free controls. Post hoc analyses revealed that the R2∗ values during menstruation were significantly higher among the pain-free controls (myometrium, P=.008; endometrium, P=.043). Although naproxen sodium increased the endometrial R2∗ values among participants with dysmenorrhea (48.29±15.78 s-1; P=.005; q=.008), it decreased myometrial R2∗ values among pain-free controls. The Doppler findings were consistent with the functional magnetic resonance imaging (-8.62±3.25 s-1; P=.008; q=.011). The pulsatility index (-0.42±0.14; P=.004; q=.004) and resistance index (-0.042±0.012; P=.001; q=.001) decreased during menses when compared with the measurements outside of menses, and the effects were significantly reversed by naproxen sodium. Naproxen sodium had the opposite effect in pain-free controls. There were no significant real-time changes in the pulsatility index, resistance index, peak systolic velocity, or minimum diastolic velocity during episodes of symptomatic menstrual cramping. CONCLUSION: Functional magnetic resonance imaging and Doppler metrics suggest that participants with dysmenorrhea have better perfusion and oxygen availability than pain-free controls. Naproxen sodium's therapeutic mechanism is associated with relative reductions in uterine perfusion and oxygen availability. An opposite pharmacologic effect was observed in pain-free controls. During menstrual cramping, there is insufficient evidence of episodic impaired uterine perfusion. Thus, prostaglandins may have protective vasoconstrictive effects in pain-free controls and opposite effects in participants with dysmenorrhea.

Dark Blood Contrast-Enhanced Brain MRI Using Echo-uT1 RESS.

BACKGROUND: The widely used magnetization-prepared rapid gradient-echo (MPRAGE) sequence makes enhancing lesions and blood vessels appear bright after gadolinium administration. However, dark blood imaging using T1-weighted Sampling Perfection with Application optimized Contrast using different flip angle Evolution (T1 SPACE) can be advantageous since it improves the conspicuity of small metastases and leptomeningeal disease. As a potential alternative to T1 SPACE, we evaluated a new dark blood sequence called echo-uT1 RESS (unbalanced T1 Relaxation-Enhanced Steady-State). PURPOSE: We compared the performance of echo-uT1 RESS with Dixon fid-uT1 RESS, MPRAGE, and T1 SPACE. STUDY TYPE: Retrospective, IRB approved. SUBJECTS/PHANTOM: Phantom to assess flow properties of echo-uT1 RESS. Twenty-one patients (14 female, age range 35-82 years) with primary and secondary brain tumors. FIELD STRENGTH/SEQUENCES: 3 Tesla/MPRAGE, T1 SPACE, Dixon fid-uT1 RESS, echo-uT1 RESS. ASSESSMENT: Flow phantom signal vs. velocity as a function of flip angle and sequence. Qualitative image assessment on 4-point scale. Quantitative evaluation of tumor-to-brain contrast, apparent contrast-to-noise ratio (aCNR), and vessel-to-brain aCNR. STATISTICAL TESTS: Friedman and Mann-Whitney U tests. A P value <0.05 was considered statistically significant. RESULTS: In the phantom, echo-uT1 RESS showed greater flow-dependent signal loss than fid-uT1 RESS. In patients, blood vessels appeared bright with MPRAGE, gray with fid-uT1 RESS, and dark with T1 SPACE and echo-uT1 RESS. For MPRAGE, Dixon fid-uT1 RESS, echo-uT1 RESS, and T1 SPACE, respective tumor-to-brain contrast values were 0.6 ± 0.3, 1.3 ± 0.5, 1.0 ± 0.4, and 0.6 ± 0.4, while normalized aCNR values were 68.9 ± 50.9, 128.4 ± 59.2, 74.2 ± 42.1, and 99.4 ± 73.9. DATA CONCLUSION: Volumetric dark blood contrast-enhanced brain MRI is feasible using echo-uT1 RESS. The dark blood effect was improved vs. fid-uT1 RESS, while both uT1 RESS versions provided better tumor-to-brain contrast than MPRAGE. Whereas T1 SPACE provided better tumor aSNR, echo-uT1 RESS provided better Weber contrast, lesion sharpness and a more consistent dark blood effect. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Feasibility of Diffusion Tensor Imaging for Decreasing Biopsy Rates in Breast Imaging: Interim Analysis of a Prospective Study.

Because of the limited specificity of diagnostic imaging, many breast lesions referred for biopsy turn out to be benign. The objective of this study was to evaluate whether diffusion tensor MRI (DTI) parametric maps can be used to safely avoid biopsy of breast lesions. Individuals referred for breast biopsy based on mammogram (MG), ultrasound (US), and/or contrast enhanced (CE)-MRI were recruited. Scans consisting of T2-weighted and DTI sequences were performed. Multiple DTI-derived parametric color maps were evaluated semi-quantitatively to characterize lesions as "definitely benign," "not definitely benign," or "suspicious." All patients subsequently underwent biopsy. In this moderately-sized prospective study, 21 out of 47 pathologically proven benign lesions were characterized by both readers as "definitely benign," which would have precluded the need for biopsy. Biopsy was recommended for 11 out of 13 cancers that were characterized as "suspicious." In the remaining two cancers and 26 of 47 benign lesions, the scans were characterized as "not definitely benign" and hence required biopsy. The main causes for "not definitely benign" scans were small lesion sizes and noise. The results suggest that in appropriately selected patients, DTI may be used to safely reduce the number of unnecessary breast biopsies.

Quantitative Blood Oxygenation Level Dependent Magnetic Resonance Imaging for Estimating Intra-renal Oxygen Availability Demonstrates Kidneys Are Hypoxemic in Human CKD.

Introduction: Kidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in evaluating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2∗ is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2∗ and renal function decline have been described, it remains uncertain to what extent R2∗ is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue. Methods: This case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured. Results: This pilot study independently measured fBV in kidney cortex (0.23 ± 0.03 vs. 0.17 ± 0.03) and medulla (0.36 ± 0.08 vs. 0.25 ± 0.03) in a small number of healthy controls (n = 7) versus CKD (n = 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 ± 0.03 vs. 0.72 ± 0.10 in cortex; 0.82 ± 0.05 vs. 0.72 ± 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 ± 6.5 vs. 38.4 ± 7.6 mm Hg in cortex; 48.4 ± 6.2 vs. 38.1 ± 4.5 mm Hg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2∗ was not. Conclusion: Our results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.

Improved Brain Tumor Conspicuity at 3 T Using Dark Blood, Fat-Suppressed, Dixon Unbalanced T1 Relaxation-Enhanced Steady-State MRI.

OBJECTIVES: Contrast-enhanced magnetic resonance imaging (MRI) is the cornerstone for brain tumor diagnosis and treatment planning. We have developed a novel dual-echo volumetric dark blood pulse sequence called Dixon unbalanced T1 relaxation-enhanced steady-state (uT 1 RESS) that improves the visibility of contrast-enhancing lesions while suppressing the tissue signals from blood vessels and fat. The purpose of this study was to test the hypothesis that Dixon uT 1 RESS would significantly improve the conspicuity of brain tumors compared with magnetization-prepared rapid gradient echo (MPRAGE), as well as to determine potential limitations of the technique. MATERIALS AND METHODS: This retrospective study was approved by the hospital institutional review board. Forty-seven adult patients undergoing an MRI scan for a brain tumor indication were included. Contrast-enhanced MRI of the brain was performed at 3 T using both MPRAGE and Dixon uT 1 RESS. To control for any impact of contrast agent washout during the scan procedure, Dixon uT 1 RESS was acquired in approximately half the subjects immediately after MPRAGE, and in the other half immediately before MPRAGE. Image quality, artifacts, and lesion detection were scored by 3 readers, whereas lesion apparent signal-to-noise ratio and lesion-to-background Weber contrast were calculated from region-of-interest measurements. RESULTS: Image quality was not rated significantly different between MPRAGE and Dixon uT 1 RESS, whereas motion artifacts were slightly worse with Dixon uT 1 RESS. Comparing Dixon uT 1 RESS with MPRAGE, the respective values for mean lesion apparent signal-to-noise ratio were not significantly different (199.31 ± 99.05 vs 203.81 ± 110.23). Compared with MPRAGE, Dixon uT 1 RESS significantly increased the tumor-to-brain contrast (1.60 ± 1.18 vs 0.61 ± 0.47 when Dixon uT1RESS was acquired before MPRAGE and 1.94 ± 0.97 vs 0.82 ± 0.55 when Dixon uT 1 RESS was acquired after MPRAGE). In patients with metastatic disease, Dixon uT 1 RESS detected at least 1 enhancing brain lesion that was missed by MPRAGE on average in 24.7% of patients, whereas Dixon uT 1 RESS did not miss any lesions that were demonstrated by MPRAGE. Dixon uT 1 RESS better detected vascular and dural invasion in a small number of patients. CONCLUSIONS: In conclusion, brain tumors were significantly more conspicuous at 3 T using Dixon uT 1 RESS compared with MPRAGE, with an approximately 2.5-fold improvement in lesion-to-background contrast irrespective of sequence order. It outperformed MPRAGE for the detection of brain metastases, dural or vascular involvement. These results suggest that Dixon uT 1 RESS could prove to be a useful adjunct or alternative to existing neuroimaging techniques for the postcontrast evaluation of intracranial tumors.

Menstrual Cycle Variation in MRI-Based Quantification of Intraluminal Gas in Women With and Without Dysmenorrhea.

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MRI) to determine colonic gas volumes throughout the menstrual cycle. To avoid dietary influence, the participants were instructed to avoid gas-producing foods before their scheduled MRI. We verified the measurement repeatability across the reviewers and obtained an intraclass correlation coefficient of 0.92. There were no significant differences in intraluminal gas volume between menses and non-menses scans (p = 0.679). Even among the women with dysmenorrhea, there was no significant difference in the intraluminal gas volume between menses and non-menses (p = 0.753). During menstruation, the participants with dysmenorrhea had less intraluminal gas than participants without dysmenorrhea (p = 0.044). However, the correlation between the bowel gas volume and the pain symptoms were not significant (p > 0.05). Although increased bowel symptoms and bloating are reported in the women with dysmenorrhea during menses, our results do not support the hypothesis that increased intraluminal gas is a contributing factor. Although dietary treatment has been shown in other studies to improve menstrual pain, the mechanism responsible for abdominal symptoms requires further investigation. Our findings demonstrate that the intraluminal bowel gas volume measurements are feasible and are unaffected by menses under a controlled diet. The method described might prove helpful in future mechanistic studies in clarifying the role of intraluminal bowel gas in other conditions.

Dark blood cardiovascular magnetic resonance of the heart, great vessels, and lungs using electrocardiographic-gated three-dimensional unbalanced steady-state free precession.

BACKGROUND: Recently, we reported a novel neuroimaging technique, unbalanced T1 Relaxation-Enhanced Steady-State (uT1RESS), which uses a tailored 3D unbalanced steady-state free precession (3D uSSFP) acquisition to suppress the blood pool signal while minimizing bulk motion sensitivity. In the present work, we hypothesized that 3D uSSFP might also be useful for dark blood imaging of the chest. To test the feasibility of this approach, we performed a pilot study in healthy subjects and patients undergoing cardiovascular magnetic resonance (CMR). MAIN BODY: The study was approved by the hospital institutional review board. Thirty-one adult subjects were imaged at 1.5 T, including 5 healthy adult subjects and 26 patients (44 to 86 years, 10 female) undergoing a clinically indicated CMR. Breath-holding was used in 29 subjects and navigator gating in 2 subjects. For breath-hold acquisitions, the 3D uSSFP pulse sequence used a high sampling bandwidth, asymmetric readout, and single-shot along the phase-encoding direction, while 3 shots were acquired for navigator-gated scans. To minimize signal dephasing from bulk motion, electrocardiographic (ECG) gating was used to synchronize the data acquisition to the diastolic phase of the cardiac cycle. To further reduce motion sensitivity, the moment of the dephasing gradient was set to one-fifth of the moment of the readout gradient. Image quality using 3D uSSFP was good-to-excellent in all subjects. The blood pool signal in the thoracic aorta was uniformly suppressed with sharp delineation of the aortic wall including two cases of ascending aortic aneurysm and two cases of aortic dissection. Compared with variable flip angle 3D turbo spin-echo, 3D uSSFP showed improved aortic wall sharpness. It was also more efficient, permitting the acquisition of 24 slices in each breath-hold versus 16 slices with 3D turbo spin-echo and a single slice with dual inversion 2D turbo spin-echo. In addition, lung and mediastinal lesions appeared highly conspicuous compared with the low blood pool signals within the heart and blood vessels. In two subjects, navigator-gated 3D uSSFP provided excellent delineation of cardiac morphology in double oblique multiplanar reformations. CONCLUSION: In this pilot study, we have demonstrated the feasibility of using ECG-gated 3D uSSFP for dark blood imaging of the heart, great vessels, and lungs. Further study will be required to fully optimize the technique and to assess clinical utility.

Near-isotropic noncontrast MRA of the renal and peripheral arteries using a thin-slab stack-of-stars quiescent interval slice-selective acquisition.

PURPOSE: Noncontrast MRA avoids potential risks from gadolinium-based contrast agents. A 2D noncontrast technique, quiescent interval slice-selective (QISS), accurately evaluates the peripheral arteries but has limited spatial resolution along the slice direction. We therefore implemented a prototype thin-slab stack-of-stars version (tsSOS-QISS) with nearly isotropic spatial resolution and tested it in the renal and peripheral arteries of healthy subjects and patients with vascular disease. METHODS: The study was approved by the hospital institutional review board. A total of 16 subjects were scanned at 1.5 T: 7 for imaging of the renal arteries and 9 for imaging of the peripheral arteries. For tsSOS-QISS of the renal arteries, each slab consisted of about sixteen 1.3-mm-thick or 2.0-mm-thick slices (interpolated to thirty-two 0.65-mm-thick or 1.0-mm-thick 3D partitions) oriented in an oblique axial or oblique coronal view along the length of the target vessel and was acquired in a breath-hold. For tsSOS-QISS of the peripheral arteries, 20 axial overlapping thin slabs were typically acquired, each with twelve 1.3-mm-thick slices (interpolated to twenty-four 0.65-mm-thick 3D partitions). Image quality, vessel sharpness in multiplanar reconstructions, and normalized SNR were measured. RESULTS: Image quality and normalized SNR in the renal and peripheral arteries were significantly better compared with 2D QISS acquired at the same spatial resolution, while vessel sharpness was improved in multiplanar reconstructions of the renal arteries. CONCLUSION: The tsSOS-QISS technique overcomes a significant limitation of 2D QISS by providing nearly isotropic spatial resolution with improved image quality, normalized SNR, and vessel sharpness in multiplanar reconstructions.