Practical applications of balanced steady-state free-precession (bSSFP) imaging in the abdomen and pelvis.

Balanced steady-state free-precession (bSSFP) is an important pulse sequence that may be underutilized in abdominal and pelvic magnetic resonance imaging (MRI). bSSFP offers several advantages for abdominal and pelvic MRI that include: bright blood effects, a relative insensitivity to the dephasing effects which occur in structures with linear movement, low specific absorption rate (SAR), high signal-to-noise ratio (SNR), high spatial resolution, and rapid acquisition times. Bright blood effects can be exploited to diagnose or confirm vascular pathologies when gadolinium-enhanced imaging cannot be performed, is indeterminate, or is degraded by artifact. The relative insensitivity to dephasing artifact in areas of linear movement is useful when imaging the biliary, urinary, and gastrointestinal tracts where dephasing artifacts may mimic filling defects such as calculi or polyps. Low SAR imaging is important in pediatric and pregnant patients and may be useful in patients with medical devices that restrict SAR levels. Rapid acquisition times and high SNR are extremely valuable assets in abdominal and pelvic MRI and bSSFP (which can be performed as static or cine acquisitions) and can be added to most existing abdominal and pelvic protocols when deemed suitable without significantly prolonging examination times. This article reviews the fundamentals of bSSFP imaging, presents vascular and nonvascular applications of bSSFP in abdominal and pelvic MRI, and discusses potential limitations (including imaging artifacts) of bSSFP. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:11-20.

Pictorial review. Magnetic resonance for radiotherapy management and treatment planning in prostatic carcinoma.

MRI has an important role for radiotherapy (RT) treatment planning in prostate cancer (PCa) providing accurate visualization of the dominant intraprostatic lesion (DIL) and locoregional anatomy, assessment of local staging and depiction of implanted devices. MRI enables the radiation oncologist to optimize RT planning by better defining target tumour volumes (thereby increasing local tumour control), as well as decreasing morbidity (by minimizing the dose to adjacent normal structures). Using MRI, radiation oncologists can define the DIL for delivery of boost doses of RT using a variety of techniques including: stereotactic body radiotherapy, intensity-modulated radiotherapy, proton RT or brachytherapy to improve tumour control. Radiologists require a familiarity with the different RT methods used to treat PCa, as well as an understanding of the advantages and disadvantages of the various MR pulse sequences available for RT planning in order to provide an optimal multidisciplinary RT treatment approach to PCa. Understanding the expected post-RT appearance of the prostate and typical characteristics of local tumour recurrence is also important because MRI is rapidly becoming an integral component for diagnosis, image-guided histological sampling and treatment planning in the setting of biochemical failure after RT or surgery.

Multi-echo gradient recalled echo imaging of the pelvis for improved depiction of brachytherapy seeds and fiducial markers facilitating radiotherapy planning and treatment of prostatic carcinoma.

PURPOSE: MR localization of implanted devices for radiotherapy (RT) in prostatic carcinoma is critical for treatment planning. This clinical note studies the application of a multi-echo gradient recalled echo (GRE) pulse sequence with sum of squares echo combination (ME GRE) to enhance detection of seeds and fiducials. MATERIALS AND METHODS: Fifteen patients who underwent MRI using fast spin echo (FSE), single-echo and ME GRE over a 9-month period were retrospectively evaluated by two readers who assessed overall image quality, depiction of seeds/fiducials and image sharpness using a 5-point scale (1 = poor, 2 = suboptimal, 3 = adequate, 4 = above average, 5 = excellent). Image scores were compared using the Wilcoxon sign rank test. RESULTS: In all 15 patients, both readers rated the depiction of seeds/fiducials with ME GRE as excellent. In all 15 patients, overall image quality and image sharpness with ME GRE was rated as excellent by reader 1. In 12/15 patients, overall image quality and image sharpness with ME GRE was rated as excellent and in the other patients above average by reader 2. There was a difference in depiction of seeds/fiducials comparing GRE to FSE (P < 0.001) and ME to single echo GRE (P < 0.001). Overall image quality and sharpness was higher with ME compared with single echo GRE (P < 0.001) and similar to FSE (P = 0.26 and P = 0.16). CONCLUSION: Multi-echo GRE provides better detection of implanted seeds and fiducial markers when compared with both FSE and single-echo GRE potentially improving RT treatment planning for prostate carcinoma.

Feasibility, detectability and clinical experience with platinum fiducial seeds for MRI/CT fusion and real-time tumor tracking during CyberKnife® stereotactic ablative radiotherapy.

BACKGROUND AND PURPOSE: The purpose of this study is to review our experience with platinum fiducials in terms of feasibility of placement and detectability by both MRI and orthogonal x-ray images used in robotic SABR.Materials and Methods: 29 consecutive SABR patients (30 tumors) treated using fiducial tracking between January 2011 and February 2012 were reviewed. A total of 108 fiducials implanted in or around various tumor sites were identified. The pixel value contrast (PVC) of fiducials seen on MRI mages and treatment unit x-ray images of patients and phantoms were analysed. RESULTS: Migration rates were similar for PS versus GS and GC (6.2%). No difference was noted between the mean PVC in cirrhotic versus non-cirrhotic liver (60.4 vs. 47.9; p = 0.074). MRI sequences for tumors in the liver and other organs revealed a mean PVC for platinum superior to that of gold (p<0.001). No PVC difference was seen between gold and platinum on analysis of the treatment unit x-rays. CONCLUSION: Platinum seeds provide a superior detectability in comparison to gold seeds or coils on MRI images and are detected equally well by an image guidance system using orthogonal x-rays, making them a better choice for fiducial-based CT-MRI registration.

Proposal of a post-prostatectomy clinical target volume based on pre-operative MRI: volumetric and dosimetric comparison to the RTOG guidelines.

BACKGROUND: Recurrence rates following radiotherapy for prostate cancer in the post-operative adjuvant or salvage setting remain substantial. Previous work from our institution demonstrated that published prostate bed CTV guidelines frequently do not cover the pre-operative MRI defined prostate. Inadequate target delineation may contribute to the high recurrence rates, but increasing target volumes may increase dose to organs at risk. METHODS: We propose guidelines for delineating post-prostatectomy target volumes based upon an individual's co-registered pre-operative MRI. MRI-based CTVs and PTVs were compared to those created using the RTOG guidelines in 30 patients. Contours were analysed in terms of absolute volume, intersection volume (Jaccard Index) and the ability to meet the RADICALS and QUANTEC rectal and bladder constraints (tomotherapy IMRT plans with PTV coverage of V98% ≥98%). RESULTS: CTV MRI was a mean of 18.6% larger than CTV RTOG: CTV MRI mean 138 cc (range 72.3 - 222.2 cc), CTV RTOG mean 116.3 cc (range 62.1 - 176.6 cc), (p < 0.0001). The difference in mean PTV was only 4.6%: PTV MRI mean 386.9 cc (range 254.4 - 551.2), PTV RTOG mean 370 cc (range 232.3 - 501.6) (p = 0.05). The mean Jaccard Index representing intersection volume between CTVs was 0.72 and 0.84 for PTVs. Both criteria had a similar ability to meet rectal and bladder constraints. Rectal DVH: 77% of CTV RTOG cases passed all RADICALS criteria and 37% all QUANTEC criteria; versus 73% and 40% for CTV MRI (p = 1.0 for both). Bladder DVH; 47% of CTV RTOG cases passed all RADICALS criteria and 67% all QUANTEC criteria, versus 57% and 60% for CTV MRI (p = 0.61for RADICALS, p = 0.79 for QUANTEC). CTV MRI spares more of the lower anterior bladder wall than CTV RTOG but increases coverage of the superior lateral bladder walls. CONCLUSION: CTV contours based upon the patient's co-registered pre-operative MRI in the post-prostatectomy setting may improve coverage of the individual's prostate bed without substantially increasing the PTV size or dose to bladder/ rectum compared to RTOG CTV guidelines. Further evaluation of whether the use of pre-operative MRI improves local control rates is warranted.

Creation of 3-dimensional prostate cancer maps: methodology and clinical and research implications.

CONTEXT: The creation of 3-dimensional prostate cancer maps could assist with surgical intervention, radiotherapy treatment planning and for correlative pathology-imaging research. OBJECTIVES: To develop methodology for creating detailed, 3-dimensional, prostate cancer maps (3DPCM) of tumor location, extra prostatic extension sites, and positive margins and to assess the adequacy of current clinical target volumes for postoperative radiotherapy to the prostate using 3DPCM coregistered with preoperative magnetic resonance imaging. DESIGN: Parallel slices of prostatectomy specimens were created with ProCUT, and 2-dimensional cancer maps were generated as line diagrams after microscopic examination of each slice. The 2-dimensional cancer maps were aligned and stacked to create a 3DPCM, which was coregistered with the preoperative magnetic resonance imaging scan. The map was exported to the radiotherapy planning system and was used to determine the areas at greater risk, which were then compared against the current Radiation Therapy Oncology Group guidelines for contouring postoperative clinical target volumes to assess the adequacy of coverage. RESULTS: Twenty-eight patients with a mean age of 66 years (range, 52-73) underwent radical prostatectomy and postoperative radiotherapy. Seventeen patients (61%) received adjuvant radiotherapy for pT3 disease and/or positive margins, and the rest underwent salvage radiotherapy. Thirty-nine percent (11 of 28) of the patients had Gleason scores of 8 or 9. The contours based on the Radiation Therapy Oncology Group guidelines for postoperative radiotherapy resulted in inadequate coverage of extraprostatic extensions in 79% (22 of 28) and positive margins in 64% (18 of 28) of the cases. CONCLUSIONS: We have developed a methodology for creation of 3DPCM. Modification of the radiotherapy contours, based on the 3DPCM coregistered with pretreatment magnetic resonance imaging, covers the areas at high risk of recurrence. The 3DPCM could become an important clinical and research tool for urologists, pathologists, radiologists, and oncologists.

Diagnostic accuracy of dual-echo (in- and opposed-phase) T1-weighted gradient recalled echo for detection and grading of hepatic iron using quantitative and visual assessment.

OBJECTIVES: Detection and quantification of hepatic iron with dual-echo gradient recalled echo (GRE) has been proposed as a rapid alternative to other magnetic resonance imaging (MRI) techniques. Co-existing steatosis and T1 weighting are limitations. This study assesses the accuracy of routine dual-echo GRE. METHODOLOGY: Between 2010 and 2013, 109 consecutive patients underwent multi-echo (ME) MRI and dual-echo GRE for quantification of hepatic iron. Liver iron concentration (LIC) was calculated from ME-MRI. Relative signal intensity (RSI) and fat signal fraction (FSF) were calculated from dual-echo GRE. Four radiologists subjectively evaluated dual-echo GRE (±subtraction). Diagnostic accuracy was compared between techniques and correlated with biopsy using Fisher's exact test, Spearman correlation and regression. RESULTS: The sensitivity of visual detection of iron ranged from 48 to 55%. Subtraction did not increase sensitivity (p < 0.001). Inter-observer variability was substantial (κ = 0.72). The specificity of visual detection of iron approached 100% with false-positive diagnoses observed using subtraction. LIC showed a higher correlation with histopathological iron grade (r = 0.94, p < 0.001) compared with RSI (r = 0.65, p = 0.02). Univariate regression showed an association between RSI and LIC (B = 0.98, p < 0.001, CI 0.73-1.23); however, the association was not significant with multi-variate regression including FSF (p = 0.28). CONCLUSIONS: Dual-echo GRE has low sensitivity for hepatic iron. Subtraction imaging can result in false-positive diagnoses. KEY POINTS: • Routine liver MRI studies cannot effectively screen patients for iron overload. • Concomitant hepatic steatosis and iron limits diagnostic accuracy of routine liver MRI. • Dual-echo GRE subtraction imaging causes false-positive diagnoses of iron overload. • Dedicated MRI techniques should be used to diagnose and quantify iron overload.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors.

UNLABELLED: ADH-1 (Exherin™) is a pentapeptide, which competitively inhibits N-cadherin, resulting in vascular disruptive effect of tumor vasculature in preclinical models. This study was designed to assess the toxicity of ADH-1 and to determine the maximal tolerated dose (MTD). PATIENTS AND METHODS: Adult patients with advanced measurable solid tumors were stratified according to their tumor N-cadherin status. ADH-1 was administered as a short infusion, every six weeks. Assessment of response was done every 6 weeks. PK parameters included: estimated volume of distribution of the central compartment, the α and ß phase half-lives, area under the plasma concentration- time curve (AUC), clearance, and volume of distribution. Target lesions were assessed by dynamic contrast enhancing- magnetic resonance imaging (DCE-MRI). RESULTS: 46 patients were enrolled, 25 (54%) had N-cadherin positive status. The doses administered ranged from 50 mg/m2 to 1000 mg/m2, and the MTD was not reached. The PK analysis of the concentration-time data displayed a biphasic profile. Most of the toxicities were grade 1 and 2 with fatigue, nausea, chest pain and dysgeusia being the most common. Eleven patients had disease control, the single patient who had partial response had N-cadherin positive tumor. CONCLUSION: ADH-1 is a well tolerated drug with a modest anti tumor effect in tumors which express N-cadherin.

Postoperative radiotherapy for prostate cancer: a comparison of four consensus guidelines and dosimetric evaluation of 3D-CRT versus tomotherapy IMRT.

PURPOSE: Despite the benefits of adjuvant radiotherapy after radical prostatectomy, approximately one-half of patients relapse. Four consensus guidelines have been published (European Organization for Research and Treatment of Cancer, Faculty of Radiation Oncology Genito-Urinary Group, Princess Margaret Hospital, Radiation Therapy Oncology Group) with the aim of standardizing the clinical target volume (CTV) delineation and improve outcomes. To date, no attempt has been made to compare these guidelines in terms of treatment volumes or organ at risk (OAR) irradiation. The extent to which the guideline-derived plans meet the dosimetric constraints of present trials or of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) trial is also unknown. Our study also explored the dosimetric benefits of intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 20 patients treated with postoperative RT were included. The three-dimensional conformal radiotherapy (3D-CRT) plans were applied to cover the guideline-generated planning target volumes (66 Gy in 33 fractions). Dose-volume histograms (DVHs) were analyzed for CTV/planning target volume coverage and to evaluate OAR irradiation. The OAR DVHs were compared with the constraints proposed in the QUANTEC and Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) trials. 3D-CRT plans were compared with the tomotherapy plans for the Radiation Therapy Oncology Group planning target volume to evaluate the advantages of IMRT. RESULTS: The CTV differed significantly between guidelines (p < 0.001). The European Organization for Research and Treatment of Cancer-CTVs were significantly smaller than the other CTVs (p < 0.001). Differences in prostate bed coverage superiorly accounted for the major volumetric differences between the guidelines. Using 3D-CRT, the DVHs rarely met the QUANTEC or RADICALS rectal constraints, independent of the guideline used. The RADICALS bladder constraints were met most often by the European Organization for Research and Treatment of Cancer consensus guideline (14 of 20). The tomotherapy IMRT plans resulted in significant OAR sparing compared with the 3D-CRT plans; however, the RADICALS and QUANTEC criteria were still missed in a large percentage of cases. CONCLUSION: Treatment volumes using the current consensus guidelines differ significantly. For the four CTV guidelines, the rectal and bladder DVH constraints proposed in the QUANTEC and RADICALS trials are rarely met with 3D-CRT. IMRT results in significant OAR sparing; however, the RADICALS dose constraints are still missed for a large percentage of cases. The rectal and bladder constraints of RADICALS should be modified to avoid a reduction in the CTVs.

The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery.

OBJECTIVE: Venous thromboembolism constitutes the leading cause of direct maternal mortality in the developed world. To date, there are no studies using magnetic resonance venography (MRV) to delineate the incidence and natural history of intraluminal filling defects in the postpartum period in patients with low thrombosis risk. STUDY DESIGN: This was a prospective cohort study of women at low thrombosis risk postvaginal delivery undergoing MRV in the early postpartum period. RESULTS: In 30 eligible and consenting participants, independently adjudicated MRV, conducted on a median of postpartum day 1, identified definite thrombosis in 30% (95% confidence interval [CI], 13.6-46.4%) of study participants. All episodes of definite thrombosis were identified in the iliac and ovarian veins. Probable thrombosis was identified in an additional 27% of study participants (95% CI, 10.3-41.7%), and possible thrombosis in an additional 10% (95% CI, 0-20.7%). CONCLUSION: In this group of low-risk postpartum patients, we identified a high prevalence of definite pelvic vein intraluminal filling defects of uncertain clinical significance. This study suggests that some degree of pelvic vein intraluminal filling defect may be a normal finding after uncomplicated vaginal delivery.

Postoperative radiotherapy in prostate cancer: the case of the missing target.

PURPOSE: Postoperative radiotherapy (XRT) increases survival in high-risk prostate cancer patients. Approximately 50% of patients on long-term follow-up relapse despite adjuvant XRT and the predominant site of failure remains local. Four consensus guidelines define postoperative clinical target volume (CTV) in prostate cancer. We explore the possibility that inadequate CTV coverage is an important cause of local failure. This study evaluates the utility of preoperative magnetic resonance imaging (MRI) in defining prostate bed CTV. METHODS AND MATERIALS: Twenty prostate cancer patients treated with postoperative XRT who also had preoperative staging MRI were included. The four guidelines were applied and the CTVs were expanded to create planning target volumes (PTVs). Preoperative MRIs were fused with postoperative planning CT scans. MRI-based prostate and gross visible tumors were contoured. Three-dimensional (3D) conformal four- and six-field XRT plans were developed and dose-volume histograms analyzed. Subtraction analysis was conducted to assess the adequacy of prostate/gross tumor coverage. RESULTS: Gross tumor was visible in 18 cases. In all 20 cases, the consensus CTVs did not fully cover the MRI-defined prostate. On average, 35% of the prostate volume and 32% of the gross tumor volume were missed using six-field 3D treatment plans. The entire MRI-defined gross tumor volume was completely covered in only two cases (six-field plans). The expanded PTVs did not cover the entire prostate bed in 50% of cases. Prostate base and mid-zones were the predominant site of inadequate coverage. CONCLUSIONS: Current postoperative CTV guidelines do not adequately cover the prostate bed and/or gross tumor based on preoperative MRI imaging. Additionally, expanded PTVs do not fully cover the prostate bed in 50% of cases. Inadequate CTV definition is likely a major contributing factor for the high risk of relapse despite adjuvant XRT. Preoperative imaging may lead to more accurate CTV definition, which should result in further improvements in survival for patients with high-risk prostate cancer.

ADH-1 in the treatment of metastatic adrenocortical carcinoma--case report.

Adrenocortical Carcinoma (ACC) is rare with an annual incidence of 0.5-2 cases per million worldwide. Some ACC tumors over express N-cadherin, which correlates with metastatic potential. ADH-1 (Exherin™) is a competitive inhibitor of N-cadherin, resulting in rapid onset of tumor vascular angiolysis and apoptosis in preclinical models. Targeting N-cadherin may cause direct anti-tumor and anti-vascular effects. We report a case of ACC with benefit from ADH-1 therapy. A 24 year old woman with an N-cadherin expressing metastatic ACC was treated on a phase I trial and treated with ADH-1 subsequently received additional doses through a special access program. The patient presented with cushingoid features from cortisol over-secretion and was diagnosed with metastatic ACC in January 2003. Tumor progression followed treatment with a combination of doxorubicin, cisplatin and mitotane. In October 2003, as a part of a phase I clinical trial she was treated with as a single dose of ADH-1 at 150 mg/m(2). This resulted in transient normalization of cortisol, tumor necrosis on CT imaging, and reduction in tumor perfusion on DCE-MRI. Following progression on several additional lines of chemotherapy, she was again treated with ADH-1 under a Special Access Program (SAP). After 33 weekly doses (22 with 150 mg/m(2) and 11 with 300 mg/m(2)) radiographic tumor progression was demonstrated and treatment discontinued. She survived 40 months with metastatic disease, dying 12 months after her last dose of ADH-1. This observation merits consideration for prospectively evaluating the efficacy of ADH-1 in patients with cortisol secreting ACC that over express N-cadherin.

Arterial input functions determined from MR signal magnitude and phase for quantitative dynamic contrast-enhanced MRI in the human pelvis.

Dynamic contrast-enhanced (DCE) MRI is often used to measure the transfer constant (Ktrans) and distribution volume (ve) in pelvic tumors. For optimal accuracy and reproducibility, one must quantify the arterial input function (AIF). Unfortunately, this is challenging due to inflow and signal saturation. A potential solution is to use MR signal phase (ϕ), which is relatively unaffected by these factors. We hypothesized that phase-derived AIFs (AIFϕ) would provide more reproducible Ktrans and ve values than magnitude-derived AIFs (AIF|S|). We tested this in 27 prostate dynamic contrast-enhanced MRI studies (echo time=2.56 ms, temporal resolution=13.5 s), using muscle as a standard. AIFϕ peak amplitude varied much less as a function of measurement location (inferior-superior) than AIF|S| (5.6±0.6 mM vs. 2.6±1.5 mM), likely as a result of ϕ inflow insensitivity. However, our main hypothesis was not confirmed. The best AIF|S| provided similar reproducibility versus AIFϕ (interpatient muscle Ktrans=0.039±0.021 min(-1) vs. 0.037±0.025 min(-1), ve=0.090±0.041 vs. 0.062±0.022, respectively).

Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section.

In the run-in phase of a thromboprophylactic trial in women at moderate to high risk of deep vein thrombosis postcesarean section, we used magnetic resonance venography and found a surprisingly high rate of pelvic deep vein thrombosis (46% overall). Pelvic magnetic resonance venography may be a useful surrogate outcome in obstetric thromboprophylaxis studies but the clinical significance is not known.

Ultrasound and MRI in the antenatal diagnosis of schizencephaly.

BACKGROUND: Schizencephaly is a brain anomaly that can be associated with severe neonatal morbidity and mortality. Precise antenatal diagnosis is critical to help families make a decision regarding the continuation of pregnancy. A sequence of magnetic resonance imaging (MRI) called HASTE (Half-Fourier Acquisition Single-Shot Turbo Spin-Echo) has been used prenatally for this purpose. CASE: We used an additional MRI sequence called true-FISP (True Fast Imaging with Steady-State Precession) to diagnose schizencephaly in a 15-year-old primigravid woman. This sequence has not been previously described in prenatal MRI. CONCLUSION: HASTE sequence provides the grey-white matter differentiation that is necessary to make the diagnosis of grey-matter-lined schizencephaly clefts. True-FISP sequence has potentially higher resolution images because it is not prone to blurring of edges and is less sensitive to flowing fluid movement. Using these two MRI sequences is essential for confirming the diagnosis of schizencephaly and can provide information regarding other commonly associated anatomic anomalies.