Transgender and nonbinary (TGNB) adolescents and young adults (AYA) designated female at birth (DFAB) experience chest dysphoria, which is associated with depression and anxiety. Top surgery may be ...performed to treat chest dysphoria.
To determine whether top surgery improves chest dysphoria, gender congruence, and body image in TGNB DFAB AYA.
This is a nonrandomized prospective cohort study of patients who underwent top surgery between December 2019 and April 2021 and a matched control group who did not receive surgery. Patients completed outcomes measures preoperatively and 3 months postoperatively. This study took place across 3 institutions in a single, large metropolitan city. Patients aged 13 to 24 years who presented for gender-affirming top surgery were recruited into the treatment arm. Patients in the treatment arm were matched with individuals in the control arm based on age and duration of testosterone therapy.
Patients in the surgical cohort underwent gender-affirming mastectomy; surgical technique was at the discretion of the surgeon.
Patient-reported outcomes were collected at enrollment and 3 months postoperatively or 3 months postbaseline for the control cohort. The primary outcome was the Chest Dysphoria Measure (CDM). Secondary outcomes included the Transgender Congruence Scale (TCS) and Body Image Scale (BIS). Baseline demographic and surgical variables were collected, and descriptive statistics were calculated. Inverse probability of treatment weighting (IPTW) was used to estimate the association of top surgery with outcomes. Probability of treatment was estimated using gradient-boosted machines with the following covariates: baseline outcome score, age, gender identity, race, ethnicity, insurance type, body mass index, testosterone use duration, chest binding, and parental support.
Overall, 81 patients were enrolled (mean SD age, 18.6 2.7 years); 11 were lost to follow-up. Thirty-six surgical patients and 34 matched control patients completed the outcomes measures. Weighted absolute standardized mean differences were acceptable between groups with respect to body mass index, but were not comparable with respect to the remaining demographic variables baseline outcome measures. Surgical complications were minimal. IPTW analyses suggest an association between surgery and substantial improvements in CDM (-25.58 points; 95% CI, -29.18 to -21.98), TCS (7.78 points; 95% CI, 6.06-9.50), and BIS (-7.20 points; 95% CI, -11.68 to -2.72) scores.
Top surgery in TGNB DFAB AYA is associated with low complication rates. Top surgery is associated with improved chest dysphoria, gender congruence, and body image satisfaction in this age group.
New magnetic resonance (MR) molecular imaging techniques offer the potential for noninvasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a ...three-dimensional dynamic dual-agent hyperpolarized
C magnetic resonance spectroscopic imaging approach with
C-pyruvate and
C-urea to investigate differences in perfusion and metabolism between low- and high-grade tumors in the transgenic adenocarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (
) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade.
values were relatively higher for high-grade TRAMP tumors. The increase in
flux correlated significantly with higher lactate dehydrogenase activity and mRNA expression of
and
as well as with more proliferative disease. There was a significant reduction in perfusion in high-grade tumors that associated with increased hypoxia and mRNA expression of
and
and increased
, attributed to increased blood vessel permeability. In 90% of the high-grade TRAMP tumors, a mismatch in perfusion and metabolism measurements was observed, with low perfusion being associated with increased
This perfusion-metabolism mismatch was also associated with metastasis. The molecular imaging approach we developed could be translated to investigate these imaging biomarkers for their diagnostic and prognostic power in future prostate cancer clinical trials.
.
Background
Hyperpolarized 13C MRI quantitatively measures enzyme‐catalyzed metabolism in cancer and metabolic diseases. Whole‐abdomen imaging will permit dynamic metabolic imaging of several ...abdominal organs simultaneously in healthy and diseased subjects.
Purpose
Image hyperpolarized 1‐13Cpyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage. Compare hyperpolarized 1‐13Cpyruvate metabolism across abdominal organs of healthy volunteers.
Study Type
Prospective technical development.
Subjects
A total of 13 healthy volunteers (8 male), 21–64 years (median 36).
Field Strength/Sequence
A 3 T. Proton: T1‐weighted spoiled gradient echo, T2‐weighted single‐shot fast spin echo, multiecho fat/water imaging. Carbon‐13: echo‐planar spectroscopic imaging, metabolite‐specific echo‐planar imaging.
Assessment
Transmit magnetic field was measured. Variations in main magnetic field (ΔB0) determined using multiecho proton acquisitions were compared to carbon‐13 acquisitions. Changes in ΔB0 were measured after localized shimming. Improvements in metabolite signal‐to‐noise ratio were calculated. Whole‐organ regions of interests were drawn over the liver, spleen, pancreas, and kidneys by a single investigator. Metabolite signals, time‐to‐peak, decay times, and mean first‐order rate constants for pyruvate‐to‐lactate (kPL) and alanine (kPA) conversion were measured in each organ.
Statistical Tests
Linear regression, one‐sample Kolmogorov–Smirnov tests, paired t‐tests, one‐way ANOVA, Tukey's multiple comparisons tests. P ≤ 0.05 considered statistically significant.
Results
Proton ΔB0 maps correlated with carbon‐13 ΔB0 maps (slope = 0.93, y‐intercept = −2.88, R2 = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean kPL and kPA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant).
Data Conclusion
Whole‐abdomen coverage with hyperpolarized carbon‐13 MRI was feasible despite technical challenges. Multiecho gradient echo 1H acquisitions accurately predicted chemical shifts observed using carbon‐13 spectroscopy. Carbon‐13 acquisitions benefited from local shimming. Metabolite energetics in the abdomen compiled for healthy volunteers can be used to design larger clinical trials in patients with metabolic diseases.
Evidence Level
2
Technical Efficacy
Stage 1
Purpose
The balanced steady‐state free precession (bSSFP) acquisition enables high spatiotemporal resolution for hyperpolarized 13C MRI at 3T but is limited by spectral contamination from adjacent ...resonances. The purpose of this study was to develop a framework for in vivo dynamic high resolution imaging of hyperpolarized 1‐13Cpyruvate and 1‐13Clactate generated in vivo at 3T by simplifying the spectrum through the use of selective suppression pulses.
Methods
Spectral suppression pulses were incorporated into the bSSFP sequence for suppression of 1‐13Calanine and 1‐13Cpyruvate‐hydrate signals, leaving only the pyruvate and lactate resonances. Subsequently, the bSSFP pulse width, time‐bandwidth, and repetition time were optimized for imaging these dual resonances.
Results
The spectral suppression reduced both the alanine and pyruvate‐hydrate signals by 85.5 ± 4.9% and had no significant effect on quantitation of pyruvate to lactate conversion (liver: P = 0.400, kidney: P = 0.499). High resolution (2 × 2 mm2 and 3 × 3 mm2) subsecond 2D coronal projections and 3D 2.5 mm isotropic images were obtained in rats and tumor‐bearing mice with 1.8–5 s temporal resolution, allowing for calculation of lactate‐to‐pyruvate ratios and kPL.
Conclusion
The developed framework presented here shows the capability for dynamic high resolution volumetric hyperpolarized bSSFP imaging of pyruvate‐to‐lactate conversion on a clinical 3T MR scanner.
MRI with hyperpolarized (HP)
C agents, also known as HP
C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has ...been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of HP agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with 1-
Cpyruvate-by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP
C-pyruvate preparation; (2) MRI system setup and calibrations; (3) data acquisition and image reconstruction; and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP
C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods and Equipment study groups. It further aims to provide a comprehensive reference for future consensus, building as the field continues to advance human studies with this metabolic imaging modality.
Purpose
To use fiducial markers containing manganese 55 to rapidly localize carbon 13 (13C) RF coils for correcting images for B1 variation.
Methods
Hollow high‐density polyethylene spheres were ...filled with 3M sodium permanganate and affixed to a rectangular 13C‐tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT. Marker positions were measured by MRI using a series of 1D projections and automated peak detection. Once the coil location was determined, coil sensitivity was estimated using a quasi‐static calculation. Simulations were performed to determine the minimum number of projections required for robust localization. Phantom experiments were used to confirm the accuracy of marker localization as well as the calculated coil sensitivity. Finally, in vivo validation was performed using hyperpolarized 13C pyruvate in a rat model.
Results
In simulations, our algorithm was accurate in determining marker positions when at least 6 projections were used (RMSE 1.4 ± 0.9 mm). These estimates were verified in phantom experiments, where markers locations were determined with an RMS accuracy of 1.3 mm. A minimum SNR of 4 was required for automated detection to perform accurately. Computed coil sensitivity had a median error of 17% when taken over the entire measured area and 5.7% over a central region. In a rat, correction for nonuniform reception and flip angle was able to normalize the signals arising from asymmetrically positioned kidneys.
Conclusion
Manganese 55 fiducial markers are an inexpensive and reliable method for rapidly localizing 13C RF coils and correcting 13C images for B1 variation without user intervention.
To use fiducial markers containing manganese 55 to rapidly localize carbon 13 (
C) RF coils for correcting images for B
variation.
Hollow high-density polyethylene spheres were filled with 3M sodium ...permanganate and affixed to a rectangular
C-tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT. Marker positions were measured by MRI using a series of 1D projections and automated peak detection. Once the coil location was determined, coil sensitivity was estimated using a quasi-static calculation. Simulations were performed to determine the minimum number of projections required for robust localization. Phantom experiments were used to confirm the accuracy of marker localization as well as the calculated coil sensitivity. Finally, in vivo validation was performed using hyperpolarized
C pyruvate in a rat model.
In simulations, our algorithm was accurate in determining marker positions when at least 6 projections were used (RMSE 1.4 ± 0.9 mm). These estimates were verified in phantom experiments, where markers locations were determined with an RMS accuracy of 1.3 mm. A minimum SNR of 4 was required for automated detection to perform accurately. Computed coil sensitivity had a median error of 17% when taken over the entire measured area and 5.7% over a central region. In a rat, correction for nonuniform reception and flip angle was able to normalize the signals arising from asymmetrically positioned kidneys.
Manganese 55 fiducial markers are an inexpensive and reliable method for rapidly localizing
C RF coils and correcting
C images for B
variation without user intervention.
Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of ...AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13C dehydroascorbate (DHA) and 13C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham‐operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13C lactate/pyruvate ratio at day 7 compared with baseline, although the 13C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham‐operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13C MRS for the non‐invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.
We have shown that hyperpolarized 13C dehydroascorbate and 13C pyruvate magnetic resonance spectroscopy can be used to non‐invasively assess the altered renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity following ischemia reperfusion injury in a murine model. Such an imaging approach can potentially enhance the prediction and monitoring of progressive kidney injury.
Hyperpolarized 13C MRI takes advantage of the unprecedented 50 000‐fold signal‐to‐noise ratio enhancement to interrogate cancer metabolism in patients and animals. It can measure the ...pyruvate‐to‐lactate conversion rate, kPL, a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate kPL reliably. In this study, three sequence components and parameters that modulate kPL estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient‐induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed that the RF‐induced magnetization spoiling can be substantially improved using an inputless kPL fitting. In vivo studies found a significantly higher apparent kPL with an additional gradient that leads to flow suppression (kPL,FID‐Delay,Crush/kPL,FID‐Delay = 1.37 ± 0.33, P < 0.01, N = 6), which agrees with simulation outcomes (12.5% kPL error with Δv = 40 cm/s), indicating that the gradients predominantly suppressed flowing pyruvate spins. Significantly lower kPL was found using a delayed free induction decay (FID) acquisition versus a minimum‐TE version (kPL,FID‐Delay/kPL,FID = 0.67 ± 0.09, P < 0.01, N = 5), and the lactate peak had broader linewidth than pyruvate (Δωlactate/Δωpyruvate = 1.32 ± 0.07, P < 0.000 01, N = 13). This illustrated that lactate's T2*, shorter than that of pyruvate, can affect calculated kPL values. We also found that an FID sequence yielded significantly lower kPL versus a double spin‐echo sequence that includes spin‐echo spoiling, flow suppression from crusher gradients, and more T2 weighting (kPL,DSE/kPL,FID = 2.40 ± 0.98, P < 0.0001, N = 7). In summary, the pulse sequence, as well as its interaction with pharmacokinetics and the tissue microenvironment, can impact and be optimized for the measurement of kPL. The data acquisition and analysis pipelines can work synergistically to provide more robust and reproducible kPL measures for future preclinical and clinical studies.
This study investigated three pulse sequence components and parameters that can affect estimates of kPL in HP‐13C MRI. In vivo animal tumor studies showed significant impact on kPL with crusher‐gradient induced flow suppression, and intrinsic image weighting due to relaxation, corroborated by signal‐model simulations. RF‐induced magnetization spoiling can be substantially improved using an inputless kPL fitting. These outcomes suggested that the pulse sequence, as well as its interaction with pharmacokinetics and tissue microenvironment, can impact the measurement of kPL.
N-(2-Acetamido)-2-aminoethanesulfonic acid (ACES), one of Good's buffers, was applied to pH imaging using hyperpolarized (13)C magnetic resonance spectroscopy. Rapid NMR- and MRI-based pH ...measurements were obtained by exploiting the sensitive pH-dependence of its (13)C chemical shift within the physiologic range.
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