Application of PET/MRI in Gynecologic Malignancies.

The diagnosis, treatment, and management of gynecologic malignancies benefit from both positron emission tomography/computed tomography (PET/CT) and MRI. PET/CT provides important information on the local extent of disease as well as diffuse metastatic involvement. MRI offers soft tissue delineation and loco-regional disease involvement. The combination of these two technologies is key in diagnosis, treatment planning, and evaluating treatment response in gynecological malignancies. This review aims to assess the performance of PET/MRI in gynecologic cancer patients and outlines the technical challenges and clinical advantages of PET/MR systems when specifically applied to gynecologic malignancies.

MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

OBJECTIVE: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids. METHODS: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded. RESULTS: The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns. CONCLUSION: MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis. CLINICAL RELEVANCE STATEMENT: Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely. KEY POINTS: • Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

Anorectal manometry for the diagnosis of pelvic floor disorders in patients with hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome.

INTRODUCTION: Functional gastrointestinal disorders (FGID) including impaired rectal evacuation are common in patients with Hypermobility Spectrum Disorder (HSD) or Hypermobile Ehlers-Danlos Syndrome (hEDS). The effect of connective tissue pathologies on pelvic floor function in HSD/hEDS remains unclear. We aimed to compare clinical characteristics and anorectal pressure profile in patients with HSD/hEDS to those of age and sex matched controls. METHODS: We conducted a retrospective review of all FGID patients who underwent high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) for evaluation of impaired rectal evacuation. Patients with HSD/hEDS were age and sex matched to a randomly selected cohort of control patients without HSD/hEDS. An abnormal BET was defined as the inability to expel a rectal balloon within 2 minutes. Wilcoxon rank sum test and Fisher's exact test were used to make comparisons and logistic regression model for predictive factors for abnormal evacuation. RESULTS: A total of 144 patients (72 with HSD/hEDS and 72 controls) were analyzed. HSD/hEDS patients were more likely to be Caucasian (p < 0.001) and nulliparous. Concurrent psychiatric disorders; depression, and anxiety (p < 0.05), and somatic syndromes; fibromyalgia, migraine and sleep disorders (p < 0.001) were more common in these patients. Rate of abnormal BET were comparable among the groups. HDS/hEDS patients had significantly less anal relaxation and higher residual anal pressures during simulated defecation, resulting in significantly more negative rectoanal pressure gradient. The remaining anorectal pressure profile and sensory levels were comparable between the groups. While diminished rectoanal pressure gradient was the determinant of abnormal balloon evacuation in non HSD/hEDS patients, increased anal resting tone and maximum volume tolerated were independent factors associated with an abnormal BET in HSD/hEDS patients. Review of defecography data from a subset of patients showed no significant differences in structural pathologies between HSD/hEDS and non HSD/hEDS patients. CONCLUSIONS: These results suggest anorectal pressure profile is not compromised by connective tissue pathologies in HSD patients. Whether concurrent psychosomatic disorders or musculoskeletal involvement impact the pelvic floor function in these patients needs further investigation.

Consensus Definitions and Interpretation Templates for Magnetic Resonance Imaging of Defecatory Pelvic Floor Disorders: Proceedings of the Consensus Meeting of the Pelvic Floor Disorders Consortium of the American Society of Colon and Rectal Surgeons, the Society of Abdominal Radiology, the International Continence Society, the American Urogynecologic Society, the International Urogynecological Association, and the Society of Gynecologic Surgeons.

The Pelvic Floor Disorders Consortium (PFDC) is a multidisciplinary organization of colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners. Specialists from these fields are all dedicated to the diagnosis and management of patients with pelvic floor conditions, but they approach, evaluate, and treat such patients with their own unique perspectives given the differences in their respective training. The PFDC was formed to bridge gaps and enable collaboration between these specialties. The goal of the PFDC is to develop and evaluate educational programs, create clinical guidelines and algorithms, and promote high quality of care in this unique patient population. The recommendations included in this article represent the work of the PFDC Working Group on Magnetic Resonance Imaging of Pelvic Floor Disorders (members listed alphabetically in Table 1). The objective was to generate inclusive, rather than prescriptive, guidance for all practitioners, irrespective of discipline, involved in the evaluation and treatment of patients with pelvic floor disorders.

Adult residual rectourethral fistula and diverticulum presenting decades after imperforate anus repair: a case report.

BACKGROUND: This report describes a rare surgical case of an intraabdominal mass in a middle-aged patient 40 years after imperforate anus repair. CASE PRESENTATION: A 44-year-old Latino male with history of repaired anorectal malformation presented with recurrent urinary tract infections and rectal prolapse with bothersome bleeding and fecal incontinence. During his preoperative evaluation, he was initially diagnosed with a prostatic utricle cyst on the basis of magnetic resonance imaging findings, which demonstrated a cystic, thick-walled mass with low signal contents that extended inferiorly to insert into the distal prostatic urethra. However, at the time of surgical resection, the thick-walled structure contained an old, firm fecaloma. The final pathology report described findings consistent with colonic tissue, suggesting a retained remnant of the original fistula and diverticulum. CONCLUSIONS: Although rare, persistent rectourethral fistula tracts and rectal diverticula after imperforate anus repair can cause symptoms decades later, requiring surgical intervention. This is an important diagnostic consideration for any adult patient with history of imperforate anus.

Data-driven self-calibration and reconstruction for non-cartesian wave-encoded single-shot fast spin echo using deep learning.

BACKGROUND: Current self-calibration and reconstruction methods for wave-encoded single-shot fast spin echo imaging (SSFSE) requires long computational time, especially when high accuracy is needed. PURPOSE: To develop and investigate the clinical feasibility of data-driven self-calibration and reconstruction of wave-encoded SSFSE imaging for computation time reduction and quality improvement. STUDY TYPE: Prospective controlled clinical trial. SUBJECTS: With Institutional Review Board approval, the proposed method was assessed on 29 consecutive adult patients (18 males, 11 females, range, 24-77 years). FIELD STRENGTH/SEQUENCE: A wave-encoded variable-density SSFSE sequence was developed for clinical 3.0T abdominal scans to enable 3.5× acceleration with full-Fourier acquisitions. Data-driven calibration of wave-encoding point-spread function (PSF) was developed using a trained deep neural network. Data-driven reconstruction was developed with another set of neural networks based on the calibrated wave-encoding PSF. Training of the calibration and reconstruction networks was performed on 15,783 2D wave-encoded SSFSE abdominal images. ASSESSMENT: Image quality of the proposed data-driven approach was compared independently and blindly with a conventional approach using iterative self-calibration and reconstruction with parallel imaging and compressed sensing by three radiologists on a scale from -2 to 2 for noise, contrast, sharpness, artifacts, and confidence. Computation time of these two approaches was also compared. STATISTICAL TESTS: Wilcoxon signed-rank tests were used to compare image quality and two-tailed t-tests were used to compare computation time with P values of under 0.05 considered statistically significant. RESULTS: An average 2.1-fold speedup in computation was achieved using the proposed method. The proposed data-driven self-calibration and reconstruction approach significantly reduced the perceived noise level (mean scores 0.82, P < 0.0001). DATA CONCLUSION: The proposed data-driven calibration and reconstruction achieved twice faster computation with reduced perceived noise, providing a fast and robust self-calibration and reconstruction for clinical abdominal SSFSE imaging. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:841-853.

Multimodal imaging assessment and histologic correlation of the female rat pelvic floor muscles' anatomy.

Pelvic floor disorders negatively impact millions of women worldwide. Although there is a strong epidemiological association with childbirth, the mechanisms leading to the dysfunction of the integral constituents of the female pelvic floor, including pelvic floor skeletal muscles, are not well understood. This is in part due to the constraints associated with directly probing these muscles, which are located deep in the pelvis. Thus, experimental models and non-invasive techniques are essential for advancing knowledge of various phenotypes of pelvic floor muscle injury and pathogenesis of muscle dysfunction, as well as developing minimally invasive approaches for the delivery of novel therapeutics. The most widely used animal model for pelvic floor disorders is the rat. However, the radiological anatomy of rat pelvic floor muscles has not been described. To remedy this gap, the current study provides the first detailed description of the female rat pelvic floor muscles' radiological appearance on MR and ultrasound images, validated by correlation with gross anatomy and histology. We also demonstrate that ultrasound guidance can be used to target rat pelvic floor muscles for possible interventional therapies.

Inversion recovery ultrashort echo time magnetic resonance imaging: A method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain - A feasibility study.

Multiple sclerosis (MS) causes demyelinating lesions in the white matter and increased iron deposition in the subcortical gray matter. Myelin protons have an extremely short T2* (<1ms) and are not directly detected with conventional clinical magnetic resonance (MR) imaging sequences. Iron deposition also reduces T2*, leading to reduced signal on clinical sequences. In this study we tested the hypothesis that the inversion recovery ultrashort echo time (IR-UTE) pulse sequence can directly and simultaneously image myelin and iron deposition using a clinical 3T scanner. The technique was first validated on a synthetic myelin phantom (myelin powder in D2O) and a Feridex iron phantom. This was followed by studies of cadaveric MS specimens, healthy volunteers and MS patients. UTE imaging of the synthetic myelin phantom showed an excellent bi-component signal decay with two populations of protons, one with a T2* of 1.2ms (residual water protons) and the other with a T2* of 290µs (myelin protons). IR-UTE imaging shows sensitivity to a wide range of iron concentrations from 0.5 to ~30mM. The IR-UTE signal from white matter of the brain of healthy volunteers shows a rapid signal decay with a short T2* of ~300µs, consistent with the T2* values of myelin protons in the synthetic myelin phantom. IR-UTE imaging in MS brain specimens and patients showed multiple white matter lesions as well as areas of high signal in subcortical gray matter. This in specimens corresponded in position to Perl's diaminobenzide staining results, consistent with increased iron deposition. IR-UTE imaging simultaneously detects lesions with myelin loss in the white matter and iron deposition in the gray matter.

Detection of in vivo enzyme activity with CatalyCEST MRI.

PURPOSE: CatalyCEST MRI compares the detection of an enzyme-responsive chemical exchange saturation transfer (CEST) agent with the detection of an unresponsive "control" CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI. METHODS: CEST agents that were responsive and unresponsive to the activity of urokinase plasminogen activator were shown to have negligible interaction with each other. A CEST-fast imaging with steady state precession (FISP) MRI protocol was used to acquire MR CEST spectroscopic images with a Capan-2 pancreatic tumor model after intravenous injection of the CEST agents. A function of (super)-Lorentzian line shapes was fit to CEST spectra of a region-of-interest that represented the tumor. RESULTS: The CEST effects from each agent showed the same initial uptake into tumor tissues, indicating that both agents had the same pharmacokinetic transport rates. Starting 5 min after injection, CEST from the enzyme-responsive agent disappeared more quickly than CEST from the unresponsive agent, indicating that the enzyme responsive agent was being catalyzed by urokinase plasminogen activator, while both agents also experienced net pharmacokinetic washout from the tumor. CONCLUSION: CatalyCEST MRI demonstrates that dynamic tracking of enzyme-responsive and unresponsive CEST agents during the same in vivo MRI study is feasible.

Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent.

The measurement of extracellular pH (pHe) has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI) contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST) was designed to measure tumor pH(e) throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb(3+)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid,10-o-aminoanilide (Yb-DO3A-oAA) suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST) effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

Improved pH measurements with a single PARACEST MRI contrast agent.

The measurement of extracellular pH has potential utility for assessing the therapeutic effects of pH-dependent and pH-altering therapies. A PARAmagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agent, Yb-DO3A-oAA, has two CEST effects that are dependent on pH. A ratio derived from these CEST effects was linearly correlated with pH throughout the physiological pH range. The pH can be measured with a precision of 0.21 pH units and an accuracy of 0.09 pH units. The pH measurement is independent of concentration and T1 relaxation times, but is dependent on temperature. Although MR coalescence affects the CEST measurements, especially at high pH, the ratiometric analysis of the CEST effects can account for incomplete saturation of the agent's amide and amine that results from MR coalescence. Provided that an empirical calibration is determined with saturation conditions, magnetic field strength and temperature that can be used for subsequent studies, these results demonstrate that this single PARACEST MRI contrast agent can accurately measure pH.

Measuring in vivo tumor pHe with CEST-FISP MRI.

Paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents have been developed that can measure pH in solution studies, but these agents have not previously been detected in vivo. To use the PARACEST agent Yb-DO3A-oAA to measure the extracellular pH (pHe) in tumor tissue, a chemical exchange saturation transfer fast imaging with steady state precession MRI protocol was developed, the saturation period was optimized for sensitive chemical exchange saturation transfer (CEST) detection, and median filtering was used to remove artifacts in CEST spectra. These improvements were used to correlate pH with a ratio of two CEST effects of Yb-DO3A-oAA at a 7 T magnetic field strength (R(2) = 0.99, standard deviation of precision = 0.011 pH units). The PARACEST agent could not be detected in tumor tissue following i.v. injection due to the low sensitivity of in vivo CEST MRI. Yb-DO3A-oAA was detected in tumor tissue and leg muscle after directly injecting the PARACEST agent into these tissues. The measured CEST effects were used to measure a tumor pH of 6.82 ± 0.21 and a leg muscle pH of 7.26 ± 0.14, and parametric pH maps were also generated from these tissue regions. These results demonstrated that tumor pHe can be measured with a PARACEST agent and a rapid CEST-MRI protocol.

A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity.

The CEST effect of many PARACEST MRI contrast agents changes in response to a molecular biomarker. However, other molecular biomarkers or environmental factors can influence CEST, so that a change in CEST is not conclusive proof for detecting the biomarker. To overcome this problem, a second control CEST effect may be included in the same PARACEST agent, which is responsive to all factors that alter the first CEST effect except for the biomarker to be measured. To investigate this approach, a PARACEST MRI contrast agent was developed with one CEST effect that is responsive to esterase enzyme activity and a second control CEST effect. The ratio of the two CEST effects was independent of concentration and T(1) relaxation, so that this agent was self-calibrating with respect to these factors. This ratiometric method was dependent on temperature and was influenced by MR coalescence as the chemical exchange rates approached the chemical shifts of the exchangable protons as temperature was increased. The two CEST effects also showed evidence of having different pH dependencies, so that this agent was not self-calibrating with respect to pH. Therefore, a self-calibrating PARACEST MRI contrast agent can more accurately detect a molecular biomarker such as esterase enzyme activity, as long as temperature and pH are within an acceptable physiological range and remain constant.

An amine-derivatized, DOTA-loaded polymeric support for Fmoc Solid Phase Peptide Synthesis.

An amine-derivatized DOTA has been used to modify the surface of a polymeric support for conventional Solid Phase Peptide Synthesis (SPPS) following standard Fmoc chemistry methods. This methodology was used to synthesize a peptide-DOTA conjugate that was demonstrated to be a PARACEST MRI contrast agent. Therefore, this synthesis methodology can facilitate Fmoc SPPS of molecular imaging contrast agents.

Monitoring infection and inflammation in murine models of cystic fibrosis with magnetic resonance imaging.

PURPOSE: To evaluate magnetic resonance imaging (MRI) in assessing lung inflammation longitudinally in genetic mouse models of cystic fibrosis (CF). MRI is used to view soft tissues noninvasively, but the lung is challenging to image. MATERIALS AND METHODS: Cftr(+/+) (wildtype) and Cftr(-/-) (CF) mice were inoculated with agarose beads laden with Pseudomonas aeruginosa. Longitudinal MR lung images were acquired with cardiac gating. The effects of echo time and respiration gating were evaluated to improve the detection of lung inflammation. RESULTS: Cardiac gating and signal averaging sufficiently suppressed motion artifacts without requiring respiration gating. MRI detected moderate to severe inflammation in infected mice, which was confirmed by histology results. CONCLUSION: In vivo longitudinal MRI methods can assess lung inflammation in P. aeruginosa-infected mice, which obviates serial sacrifice. MRI was able to detect inflammation in the absence of other physiological symptoms.