Background

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been used to study perfusion in a wide variety of soft tissues including the bone marrow. Study of perfusion in hard tissues such as cortical bone has been much more limited because of the lack of detectable MR signal from them using conventional pulse sequences. However, two-dimensional (2D) ultrashort echo time (UTE) sequences detect signal from cortical bone and allow fast imaging of this tissue. In addition, adiabatic 2D inversion recovery UTE (IR-UTE) sequences can provide excellent signal suppression of soft tissues, such as muscle and marrow, and allow cortical bone to be seen with high contrast and reduced artefacts. We aimed to assess the feasibility of using 2D UTE and 2D IR-UTE sequences to perform DCE-MRI in the cortical bone of rabbits and human volunteers.

Methods

Cortical bone perfusion was studied in rabbits (n=12) and human volunteers (n=3) using 2D UTE and 2D IR-UTE sequences on a clinical 3T scanner. Dynamic data with an in-plane resolution of ~0.5×0.5 mm², single slice thickness of 3 mm for rabbits and 10 mm for human volunteers, and temporal resolution of 23 s for 2D UTE imaging of rabbits, 28 s for 2D UTE imaging of human volunteers, and 60 s for 2D IR-UTE imaging of both the rabbits and human volunteers were acquired before and after the injection of a Gd contrast agent (Gd-BOPTA: Multihance; Bracco Imaging SpA, Milan, Italy). The dose was 0.06 mmol/kg for rabbits and 0.2 mmol/kg for human subjects. Kinetic analyses based on the Brix model, as well as simple calculations of maximum enhancement (ME) and enhancement slope (ES), were performed.

Results

The 12 rabbits showed a mean K^trans of 0.36±0.07 min^-1, K_ep of 8.42±3.17 min^-1, ME of 28.30±6.83, ES of 0.35±0.18 for the femur with the 2D UTE sequence, and a mean K^trans of 0.45±0.10 min^-1, K_ep of 9.80±0.50 min^-1, ME of 48.84±12.12, and ES of 0.69±0.27 for the femur with the 2D IR-UTE sequence. Lower ME and ES values were observed in the tibial midshaft of healthy human volunteers compared to rabbits.

Conclusions

These results show that 2D UTE and 2D IR-UTE sequences are capable of detecting dynamic contrast enhancement in cortical bone in both rabbits and healthy human volunteers. Clinical studies with these techniques are likely to be feasible.

BACKGROUND AND PURPOSE: Intravoxel-incoherent-motion (IVIM) magnetic-resonance-imaging (MRI) and positron-emission-tomography (PET) have been investigated independently but not voxel-wise to evaluate tumor microenvironment in cervical carcinoma patients. Whether regionally combined information of IVIM and PET offers additional predictive benefit over each modality independently has not been explored. Here, we investigated parametric-response-mapping (PRM) of co-registered PET and IVIM in cervical cancer patients to identify sub-volumes that may predict tumor shrinkage to concurrent-chemoradiation-therapy (CCRT). MATERIALS AND METHODS: Twenty cervical cancer patients (age: 63[41-85]) were retrospectively evaluated. Diffusion-weighted-images (DWIs) were acquired on 3.0 T MRIs using a free-breathing single-shot-spin echo-planar-imaging (EPI) sequence. Pre- and on-treatment (∼after four-weeks of CCRT) MRI and pre-treatment FDG-PET/CT were acquired. IVIM model-fitting on the DWIs was performed using a Bayesian-fitting simplified two-compartment model. Three-dimensional rigidly-registered maps of PET/CT standardized-uptake-value (SUV) and IVIM diffusion-coefficient (D) and perfusion-fraction (f) were generated. Population-means of PET-SUV, IVIM-D and IVIM-f from pre-treatment-scans were calculated and used to generate PRM via a voxel-wise joint-histogram-analysis to classify voxels as high/low metabolic-activity and with high/low (hi/lo) cellular-density. Similar PRM maps were generated for SUV and f. RESULTS: Tumor-volume (p < 0.001) significantly decreased, while IVIM-f (p = 0.002) and IVIM-D (p = 0.03) significantly increased on-treatment. Pre-treatment tumor-volume (r = -0.45,p = 0.04) and PRM-SUVhi D lo (r = -0.65,p = 0.002) negatively correlated with ΔGTV, while pre-treatment IVIM-D (r = 0.64,p = 0.002), PRM-SUVlo f hi (r = 0.52,p = 0.02), and PRM-SUVlo D hi (r = 0.74,p < 0.001) positively correlated with ΔGTV. CONCLUSION: IVIM and PET was performed on cervical cancer patients undergoing CCRT and we observed that both IVIM-f and IVIM-D increased during treatment. Additionally, PRM was applied, and sub-volumes were identified that were related to ΔGTV.

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.

Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32 ± 0.09 ms, and a short mean T1 of 226 ± 46 ms were demonstrated for the healthy volunteers at 3T.

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.

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.

OBJECTIVES: We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR). MATERIALS AND METHODS: We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20 cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using χ 2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis. RESULTS: One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage ( P <0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6% , P =0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF ( P =0.05). CONCLUSIONS: Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.

Purpose

Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e., 150-200/year) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKI). Lack of human models for any SDH-mutant tumors, including GIST, has limited molecular characterization and drug discovery.

Experimental design

We describe methods for establishing novel patient-derived SDH-mutant (mSDH) GIST models and interrogated the efficacy of temozolomide on these tumor models in vitro and in clinical trials of patients with mSDH GIST.

Results

Molecular and metabolic characterization of our patient-derived mSDH GIST models revealed that these models recapitulate the transcriptional and metabolic hallmarks of parent tumors and SDH deficiency. We further demonstrate that temozolomide elicits DNA damage and apoptosis in our mSDH GIST models. Translating our in vitro discovery to the clinic, a cohort of patients with SDH-mutant GIST treated with temozolomide (n = 5) demonstrated a 40% objective response rate and 100% disease control rate, suggesting that temozolomide represents a promising therapy for this subset of GIST.

Conclusions

We report the first methods to establish patient-derived mSDH tumor models, which can be readily employed for understanding patient-specific tumor biology and treatment strategies. We also demonstrate that temozolomide is effective in patients with mSDH GIST who are refractory to existing chemotherapeutic drugs (namely, TKIs) in clinic for GISTs, bringing a promising treatment option for these patients to clinic.See related commentary by Blakely et al., p. 3.