Close encounters of the blurred kind.

We present a visually arresting scout image obtained during a CT head scan of an elderly patient for assessment of new onset confusion. The patient moved during the scout image acquisition resulting in distortion of the cranial vault that never the less remained largely in focus.

Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is the deadliest skin cancer, with an increasing incidence and mortality rate. Currently, staging of patients with primary melanoma is performed using histological biomarkers such as tumor thickness and ulceration. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, we aimed to identify novel biomarkers providing additional clinical information over current factors using unbiased genome-wide DNA methylation analyses. METHODS: We performed a comprehensive DNA methylation analysis during all progression stages of melanoma using Infinium HumanMethylation450 BeadChips on a discovery cohort of benign nevi (n = 14) and malignant melanoma from both primary (n = 33) and metastatic (n = 28) sites, integrating the DNA methylome with gene expression data. We validated the discovered biomarkers in three independent validation cohorts by pyrosequencing and immunohistochemistry. RESULTS: We identified and validated biomarkers for, and pathways involved in, melanoma development (e.g., HOXA9 DNA methylation) and tumor progression (e.g., TBC1D16 DNA methylation). In addition, we determined a prognostic signature with potential clinical applicability and validated PON3 DNA methylation and OVOL1 protein expression as biomarkers with prognostic information independent of tumor thickness and ulceration. CONCLUSIONS: Our data underscores the importance of epigenomic regulation in triggering metastatic dissemination through the inactivation of central cancer-related pathways. Inactivation of cell-adhesion and differentiation unleashes dissemination, and subsequent activation of inflammatory and immune system programs impairs anti-tumoral defense pathways. Moreover, we identify several markers of tumor development and progression previously unrelated to melanoma, and determined a prognostic signature with potential clinical utility.

Accelerated dual-venc 4D flow MRI for neurovascular applications.

PURPOSE: To improve velocity-to-noise ratio (VNR) and dynamic velocity range of 4D flow magnetic resonance imaging (MRI) by using dual-velocity encoding (dual-venc) with k-t generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. MATERIALS AND METHODS: A dual-venc 4D flow MRI sequence with k-t GRAPPA acceleration was developed using a shared reference scan followed by three-directional low- and high-venc scans (repetition time / echo time / flip angle = 6.1 msec / 3.4 msec / 15°, temporal/spatial resolution = 43.0 msec/1.2 × 1.2 × 1.2 mm3 ). The high-venc data were used to correct for aliasing in the low-venc data, resulting in a single dataset with the favorable VNR of the low-venc but without velocity aliasing. The sequence was validated with a 3T MRI scanner in phantom experiments and applied in 16 volunteers to investigate its feasibility for assessing intracranial hemodynamics (net flow and peak velocity) at the major intracranial vessels. In addition, image quality and image noise were assessed in the in vivo acquisitions. RESULTS: All 4D flow MRI scans were acquired successfully with an acquisition time of 20 ± 4 minutes. The shared reference scan reduced the total acquisition time by 12.5% compared to two separate scans. Phantom experiments showed 51.4% reduced noise for dual-venc compared to high-venc and an excellent agreement of velocities (ρ = 0.8, P < 0.001). The volunteer data showed decreased noise in dual-venc data (54.6% lower) compared to high-venc, and improved image quality, as graded by two observers: fewer artifacts (P < 0.0001), improved vessel conspicuity (P < 0.0001), and reduced noise (P < 0.0001). CONCLUSION: Dual-venc 4D flow MRI exhibits the superior VNR of the low-venc acquisition and reliably incorporates low- and high-velocity fields simultaneously. In vitro and in vivo data demonstrate improved flow visualization, image quality, and image noise. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:102-114.

Quiescent interval low angle shot magnetic resonance angiography of the extracranial carotid arteries.

PURPOSE: To test the feasibility of a quiescent interval low-angle shot (QLASH) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries at 3 T. METHODS: The extracranial carotid arteries were imaged using QLASH MRA in healthy volunteers and patients with carotid arterial disease. The impact of three gating strategies (electrocardiographic-gated, pulse-gated, ungated) was evaluated. Image quality comparisons were made with respect to two-dimensional (2D) time of flight (TOF) MRA in volunteers and patients and contrast-enhanced MRA (CEMRA) in patients. Stenoses in patients were graded. RESULTS: QLASH MRA displayed the entire extent of the extracranial carotid arteries from their origins to the skull base. Electrocardiographic-gated QLASH MRA provided better image quality than pulse-gated and ungated implementations (P < 0.05) as well as 2D TOF MRA (P < 0.05). For grading of disease, QLASH MRA showed almost perfect agreement with CEMRA (Cohen's kappa = 0.86, P < 0.001) in a small cohort of patients with carotid arterial stenosis. CONCLUSION: QLASH MRA allows for evaluation of the entire extent of the extracranial carotid arteries with an average scan time of less than 6 min and better image quality than 2D TOF. Initial clinical results in this pilot study suggest that QLASH has potential utility as a nonenhanced alternative to CEMRA.

Arterial spin labeled carotid MR angiography: A phantom study examining the impact of technical and hemodynamic factors.

PURPOSE: To quantify the accuracy of three-dimensional (3D) radial arterial spin labeled (ASL) magnetic resonance angiography (MRA) using vascular models of carotid stenosis. METHODS: Eight vascular models were imaged at 1.5 Tesla using pulsatile flow waveforms at rates found in the internal carotid arteries (100-400 mL/min). The impacts of the 3D ASL imaging readout (fast low angle shot (FLASH) versus balanced steady-state free precession (bSSFP)), ultrashort echo time imaging using a pointwise encoding time reduction with radial acquisition (PETRA), and model stenosis severity on the accuracy of vascular model display at the location of stenosis were quantified. Accuracy was computed vis-à-vis a reference bSSFP volume acquired under no flow. Comparisons were made with standard-of-care contrast-enhanced MRA (CEMRA) and Cartesian time-of-flight (TOF) MRA protocols. RESULTS: For 50% and 70% stenoses, CEMRA was most accurate (respective accuracies of 81.7% and 78.6%), followed by ASL FLASH (75.7% and 71.8%), ASL PETRA (69.6% and 70.6%), 3D TOF (66.6% and 57.1%), ASL bSSFP (68.7% and 51.2%), and 2D TOF (65.1% and 50.6%). CONCLUSION: Flow phantom imaging studies show that ASL MRA can improve the display of hemodynamically significant carotid arterial stenosis compared with TOF MRA, with FLASH and ultrashort echo time readouts being most accurate.

Nonenhanced hybridized arterial spin labeled magnetic resonance angiography of the extracranial carotid arteries using a fast low angle shot readout at 3 Tesla.

BACKGROUND: To evaluate ungated nonenhanced hybridized arterial spin labeling (hASL) magnetic resonance angiography (MRA) of the extracranial carotid arteries using a fast low angle shot (FLASH) readout at 3 Tesla. METHODS: In this retrospective, institutional review board-approved and HIPAA-compliant study, we evaluated the image quality (4-point scale) of nonenhanced hASL MRA using a FLASH readout with respect to contrast-enhanced MRA (CEMRA) in 37 patients presenting with neurologic symptoms. Two certified neuroradiologists independently evaluated 407 arterial segments (11 per patient) for image quality. The presence of vascular pathology was determined by consensus reading. Gwet's AC1 was used to assess inter-rater agreement in image quality scores, and image quality scores were correlated with age and body mass index. Objective measurements of arterial lumen area and sharpness in the carotid arteries were compared to values obtained with CEMRA. Comparisons were also made with conventional nonenhanced 2D time-of-flight (TOF) MRA. RESULTS: CEMRA provided the best image quality, while nonenhanced hASL FLASH MRA provided image quality that exceeded 2D TOF at the carotid bifurcation and in the internal and external carotid arteries. All nine vascular abnormalities of the carotid and intracranial arteries detected by CEMRA were depicted with hASL MRA, with no false positives. Inter-rater agreement of image quality scores was highest for CEMRA (AC1 = 0.87), followed by hASL (AC1 = 0.61) and TOF (AC1 = 0.43) (P < 0.001, all comparisons). With respect to CEMRA, agreement in cross-sectional lumen area was significantly better with hASL than TOF in the common carotid artery (intraclass correlation (ICC) = 0.90 versus 0.66; P < 0.05) and at the carotid bifurcation (ICC = 0.87 versus 0.54; P < 0.05). Nonenhanced hASL MRA provided superior arterial sharpness with respect to CEMRA and 2D TOF (P < 0.001). CONCLUSION: Although inferior to CEMRA in terms of image quality and inter-rater agreement, hASL FLASH MRA offers an alternative to 2D TOF for the nonenhanced evaluation of the extracranial carotid arteries at 3 Tesla. Compared with 2D TOF, nonenhanced hASL FLASH MRA provides improved quantification of arterial cross-sectional area, vessel sharpness, inter-rater agreement and image quality.

Ungated radial quiescent-inflow single-shot (UnQISS) magnetic resonance angiography using optimized azimuthal equidistant projections.

PURPOSE: We hypothesized that non-contrast-enhanced MR angiography (NEMRA) could be performed without cardiac gating by using a variant of the quiescent-inflow single-shot (QISS) technique. METHODS: Ungated QISS (UnQISS) MRA was evaluated in eight patients with peripheral arterial disease at 1.5T. The radial acquisition used optimized azimuthal equidistant projections, a long quiescent inflow time (1200 ms) to ensure replenishment of saturated in-plane spins irrespective of the cardiac phase, and a lengthy readout (1200 ms) so that a complete cardiac cycle was sampled for each slice. Venous and background tissue suppression was obtained using frequency-offset-corrected inversion radiofrequency pulses. RESULTS: Scan time for UnQISS was 15.4 min for an eight-station whole-leg acquisition. The appearance of UnQISS MRA acquired using the body coil was comparable to electrocardiographic-gated QISS MRA using phased array coils. A small radial view angle increment minimized eddy current-related artifacts, whereas image quality was inferior with a golden view angle radial increment or Cartesian trajectory. In patient studies, ≥50% stenoses were consistently detected. CONCLUSION: Using UnQISS, peripheral NEMRA can be performed without the need for cardiac gating. The use of fixed imaging parameters and body coil for signal reception further simplifies the scan procedure.

Motorised mobility scooters; upper limb fractures in elderly novice users.

We describe three upper limb injuries admitted in one year to our institution resulting from falls from motorised mobility scooters (MMS) where all three users were novices, using their MMS for less than 6 weeks. They sustained injuries in close proximity to their homes, necessitating admission to hospital. None had received any formal training before commencing use of their respective devices. Use of MMS devices increases independence in mobility, enhances quality of life, improves self-esteem, facilitating social participation in everyday life. Use of these devices is not without risks, and no clear safety guidelines or competency testing exists for users. We believe these injuries in novice users highlights this deficiency, and should alert prescribers of these devices to advocate some form of driver training for new users.

Tumor profiling using protein biomarker panels in malignant melanoma: application of tissue microarrays and beyond.

Despite advances in our knowledge of the disease, malignant melanoma remains an unpredictable entity. The revolution in molecular biological techniques, such as DNA sequencing and gene-expression profiling, has uncovered many potential protein targets and biomarkers relevant to melanoma progression. Successful clinical application would be aided significantly by downstream proteomic validation of those candidate markers using a combination of immunohistochemistry and tissue microarrays. Yet, research in this context seems to lag behind the output of genomic data relating to melanoma. In this article, we look at the strengths and pitfalls of tissue microarrays in malignant melanoma. We will show how tissue microarrays have become a vital step in the transition from molecular techniques to useful clinical assays and interventions and look at likely future developments for advances in this field.

MRI-directed cognitive fusion-guided biopsy of the anterior prostate tumors.

PURPOSE: We aimed to evaluate the efficacy of magnetic resonance imaging (MRI)-directed cognitive fusion transrectal ultrasonography (TRUS)-guided anterior prostate biopsy for diagnosis of anterior prostate tumors and to illustrate this technique. METHODS: A total of 39 patients with previous negative TRUS biopsy, but high clinical suspicion of occult prostate cancer, prospectively underwent prostate MRI including diffusion-weighted imaging (DWI). Patients with a suspicious anterior lesion on MRI underwent targeted anterior gland TRUS-guided biopsy with cognitive fusion technique using sagittal probe orientation. PIRADS version 1 scores (T2, DWI, and overall), lesion size, prostate-specific antigen (PSA), PSA density, and prostate gland volume were compared between positive and negative biopsy groups and between clinically significant cancer and remaining cases. Logistic regression analysis of imaging parameters and prostate cancer diagnosis was performed. RESULTS: Anterior gland prostate adenocarcinoma was diagnosed in 18 patients (46.2%) on targeted anterior gland TRUS-guided biopsy. Clinically significant prostate cancer was diagnosed in 13 patients (33.3%). MRI lesion size, T2, DWI, and overall PIRADS scores were significantly higher in patients with positive targeted biopsies and those with clinically significant cancer (P < 0.05). Biopsies were positive in 90%, 33%, and 29% of patients with overall PIRADS scores of 5, 4, and 3 respectively. Overall PIRADS score was an independent predictor of all prostate cancer diagnosis and of clinically significant prostate cancer diagnosis. CONCLUSION: Targeted anterior gland TRUS-guided biopsy with MRI-directed cognitive fusion enables accurate sampling and may improve tumor detection yield of anterior prostate cancer.

Congenital heart disease in adults: Quantitative and qualitative evaluation of IR FLASH and IR SSFP MRA techniques using a blood pool contrast agent in the steady state and comparison to first pass MRA.

OBJECTIVES: To evaluate magnetic resonance angiography sequences during the contrast steady-state (SS-MRA) using inversion recovery (IR) with fast low-angle shot (IR-FLASH) or steady-state free precession (IR-SSFP) read-outs, following the injection of a blood-pool contrast agent, and compare them to first-pass MR angiography (FP-MRA) in adults with congenital heart disease (CHD). MATERIALS AND METHODS: Twenty-three adult patients with CHD who underwent both SS-MRA and FP-MRA using a 1.5-T scanner were retrospectively identified. Signal-to-noise and contrast-to-noise ratios were obtained at eight locations within the aorta and pulmonary vessels.. Image quality and the presence of artifacts were subjectively assessed by two radiologists. The presence of pathology was noted and given a confidence score. RESULTS: There was no difference in vessel dimensions among the sequences. IR-SSFP showed better image quality and fewer artifacts than IR-FLASH and FP-MRA. Confidence scores were significantly higher for SS-MRA compared to FP-MRA. Seven cases (30.4%) had findings detected at SS-MRA that were not detected at FP-MRA, and 2 cases (8.7%) had findings detected by IR-SSFP only. CONCLUSION: SS-MRA of the thoracic vasculature using a blood pool contrast agent offers superior image quality and reveals more abnormalities compared to standard FP-MRA in adults with CHD, and it is best achieved with an IR-SSFP sequence. These sequences could lead to increased detection rates of abnormalities and provide a simpler protocol image acquisition.

P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.

Metastases are the major cause of death from melanoma, a skin cancer that has the fastest rising incidence of any malignancy in the Western world. Molecular pathways that drive melanoblast migration in development are believed to underpin the movement and ultimately the metastasis of melanoma. Here we show that mice lacking P-Rex1, a Rac-specific Rho GTPase guanine nucleotide exchange factor, have a melanoblast migration defect during development evidenced by a white belly. Moreover, these P-Rex1(-/-) mice are resistant to metastasis when crossed to a murine model of melanoma. Mechanistically, this is associated with P-Rex1 driving invasion in a Rac-dependent manner. P-Rex1 is elevated in the majority of human melanoma cell lines and tumour tissue. We conclude that P-Rex1 has an important role in melanoblast migration and cancer progression to metastasis in mice and humans.

Analysis of patients with false negative mammography and symptomatic breast carcinoma.

AIM: False-negative mammograms may result in a delay in breast carcinoma diagnosis and have important implications for patient care. In this study, the characteristics of symptomatic patients with false-negative mammograms were analysed. METHODS: Patients with symptomatic breast carcinoma were identified over a 10-year period (1994-2004). One hundred and twenty-four patients had false-negative preoperative mammograms and 1241 patients had abnormal preoperative mammograms. Clinical presentation, diagnostic methods and pathology were analysed. False-negative mammograms were reviewed by a specialist breast radiologist. RESULTS: Following retrospective review, 42% of false-negative mammograms were re-categorised as suspicious. The most commonly misinterpreted lesion was architectural distortion/asymmetrical density. Adjuvant ultrasound, where performed (n = 27), raised the level of suspicion in 93% of cases. Patients with false-negative mammograms were more likely to be younger (P < 0.0001), present with nipple discharge (P = 0.002) and have smaller tumours (P < 0.0001). Their tumours were more frequently located outside the upper outer quadrant (P = 0.002). False-negative mammography led to a delay in diagnosis of >2 months in 12 patients. CONCLUSION: Symptomatic patients with false-negative mammograms often demonstrate definite abnormalities on imaging, the most common of which is architectural distortion/asymmetrical density. Those at particular risk were younger patients, those with nipple discharge, and patients with lesions located outside the upper outer quadrant.