Shonit Punwani

Standards of Reporting for MRI-targeted Biopsy Studies (START) of the Prostate: Recommendations from an International Working Group.

BACKGROUND A systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies. OBJECTIVE To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). DESIGN, SETTING, AND PARTICIPANTS Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist). RESULTS AND LIMITATIONS The strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies. CONCLUSIONS Use of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.

Mural Inflammation in Crohn Disease: Location-Matched Histologic Validation of MR Imaging Features

PURPOSE To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference. MATERIALS AND METHODS Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate. RESULTS AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS. CONCLUSION Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.

Mural Crohn Disease: Correlation of Dynamic Contrast-enhanced MR Imaging Findings with Angiogenesis and Inflammation at Histologic Examination—Pilot Study

PURPOSE To determine mural perfusion dynamics in Crohn disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to correlate these with histopathologic markers of inflammation and angiogenesis. MATERIALS AND METHODS Ethical permission was given by the University College London Hospital ethics committee, and informed consent was obtained from all participants. Eleven consecutive patients with Crohn disease (eight female patients, three men; mean age, 39.5 years; range, 16.4-66.6 years) undergoing elective small-bowel resection were recruited between July 2006 and December 2007. Harvey-Bradshaw index, C-reactive protein (CRP) level, and disease chronicity were recorded. Preoperatively, dynamic contrast-enhanced MR imaging was performed through the section of bowel destined for resection, and slope of enhancement, time to maximum enhancement, enhancement ratio, the volume transfer coefficient K(trans), and the extracellular volume fraction v(e) were calculated for the affected segment. Ex vivo surgical specimens were imaged to facilitate imaging-pathologic correlation. Histopathologic sampling of the specimen was performed through the imaged tissue, and microvascular density (MVD) was determined, together with acute and chronic inflammation scores. Correlations between clinical, MR imaging, and histopathologic data were made by using the Kendall rank correlation and linear regression. RESULTS Disease chronicity was positively correlated with enhancement ratio (correlation coefficient, 0.82; P = .002). Slope of enhancement demonstrated a significant negative correlation with MVD (correlation coefficient, -0.86; P < .001). There was a negative correlation between CRP level and slope of enhancement (correlation coefficient, -0.77; P = .006). Neither acute nor chronic inflammation score correlated with any other parameter. CONCLUSION Certain MR imaging-derived mural hemodynamic parameters correlate with disease chronicity and angiogenesis in Crohn disease, but not with histologic and clinical markers of inflammation. Data support the working hypothesis that microvessel permeability increases with disease chronicity and that tissue MVD is actually inversely related to mural blood flow.

Pediatric and Adolescent Lymphoma: Comparison of Whole-Body STIR Half-Fourier RARE MR Imaging with an Enhanced PET/CT Reference for Initial Staging

PURPOSE To compare the diagnostic performance of rapid whole-body anatomic magnetic resonance (MR) staging of pediatric and adolescent lymphoma to an enhanced positron emission tomographic (PET)/computed tomographic (CT) reference standard. MATERIALS AND METHODS Ethical permission was given by the University College London Hospital ethics committee, and informed written consent was obtained from all participants and/or parents or guardians. Thirty-one subjects (age range, 7.3-18.0 years; 18 male, 11 female) with histologically proved lymphoma were prospectively recruited. Pretreatment staging was performed with whole-body short inversion time inversion-recovery (STIR) half-Fourier rapid acquisition with relaxation enhancement (RARE) MR imaging, fluorine 18 fluorodeoxyglucose PET/CT, and contrast agent-enhanced chest CT. Twenty-six subjects had posttreatment PET/CT and compromised our final cohort. Eleven nodal and 11 extranodal sites per patient were assessed on MR imaging by two radiologists in consensus, with a nodal short-axis threshold of >1 cm and predefined extranodal positivity criteria. The same sites were independantly evaluated by two nuclear medicine physicians on PET/CT images. Disease positivity was defined as a maximum standardized uptake value >2.5 or nodal size >1 cm. An unblinded expert panel reevaluated the imaging findings, removing perceptual errors, and derived an enhanced PET/CT reference standard (taking into account chest CT and 3-month follow-up imaging) against which the reported and intrinsic performance of MR imaging was assessed by using the kappa statistic. RESULTS There was very good agreement between MR imaging and the enhanced PET/CT reference standard for nodal and extranodal staging (kappa = 0.96 and 0.86, respectively) which improved following elimination of perceptual errors (kappa = 0.97 and 0.91, respectively). The sensitivity and specificity of MR imaging (following removal of perceptual error) were 98% and 99%, respectively, for nodal disease and 91% and 99%, respectively, for extranodal disease. CONCLUSION Whole-body STIR half-Fourier RARE MR imaging of pediatric and adolescent lymphoma can accurately depict nodal and extranodal disease and may provide an alternative nonionizing imaging method for anatomic disease assessment at initial staging.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography–guided biopsy for prostate‐cancer detection in men with a raised prostate‐specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography–guided biopsy. Men in the MRI‐targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10‐to‐12–core, transrectal ultrasonography–guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI‐targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI‐targeted biopsy group, as compared with 64 of 248 (26%) in the standard‐biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI‐targeted biopsy group than in the standard‐biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, ‐13 percentage points; 95% CI, ‐19 to ‐7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI‐targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027.)

Scoring systems used for the interpretation and reporting of multiparametric MRI for prostate cancer detection, localization, and characterization: could standardization lead to improved utilization of imaging within the diagnostic pathway?

Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used earlier in the prostate cancer diagnostic pathway in order to detect and localize disease. Its results can be used to help decide on the indication, type, and localization of a prostate biopsy for cancer diagnosis. In addition, mpMRI has the potential to contribute information on the characterization, or aggressiveness, of detected cancers including tumor progression over time. There is considerable variation in the way results of different MRI sequences are reported. We conducted a review of scoring systems that have been used in the detection and characterization of prostate cancer. This revealed that existing scoring and reporting systems differ in purpose, scale, and range. We evaluate these differences in this review. This first step in collating all methods of scoring and reporting mpMRI will ultimately lead to consensus approaches to develop a standardized reporting scheme that can be widely adopted and validated to ensure comparability of research outputs and optimal clinical practice. J. Magn. Reson. Imaging 2013;37:48–58.

Quantified terminal ileal motility during MR enterography as a potential biomarker of Crohn’s disease activity: a preliminary study

AbstractObjectiveTo compare quantified terminal ileal (TI) motility during MR enterography (MRE) with histopathological severity of acute inflammation in Crohn’s disease.MethodsA total of 28 Crohn’s patients underwent MRE and endoscopic TI biopsy. Axial and coronal TrueFISP, HASTE and post-gadolinium VIBE images were supplemented by multiple coronal TrueFISP cine motility sequences through the small bowel volume. TI motility index (MI) was quantified using validated software; an acute inflammation score (eAIS; 0–6) was assigned to the biopsy. Two observers qualitatively scored mural thickness, T2 signal, contrast enhancement and perimural oedema (0–3) to produce an activity score (aMRIs) based on anatomical MRI. The association among the MI, eAIS and aMRIs was tested using Spearman’s rank correlation. Wilcoxon rank sum test compared motility in subjects with and without histopathological inflammation.ResultsMean MI and mean eAIS were 0.27 (range 0.06–0.55) and 1.5 (range 0–5), respectively. There was a significant difference in MI between non-inflamed (mean 0.37, range 0.13–0.55) and inflamed (mean 0.19, range 0.06–0.44) TI, P = 0.002, and a significant negative correlation between MI and both eAIS (Rho = −0.52, P = 0.005) and aMRIs (R = −0.7, P < 0.001).ConclusionQuantified TI motility negatively correlates with histopathological measures of disease activity and existing anatomical MRI activity biomarkers.Key Points• Magnetic resonance imaging is increasingly used to assess Crohn’s disease. • MRI measurements can provide a quantitative assessment of small bowel motility. • MR enterography can grade Crohn’s disease. • Small bowel motility can be used as a marker of inflammatory activity.

MRI measurements of cerebral deoxyhaemoglobin concentration [dHb] - correlation with near infrared spectroscopy (NIRS)

Changes in physiological parameters such as cerebral blood flow, cerebral blood volume, oxygen extraction, and the size and distribution of cerebral blood vessels, result in changes in the local concentration of deoxyhaemoglobin ([dHb]). The purpose of this study was to quantitatively investigate the dependence of the R2* relaxation rate upon the [dHb] per voxel. Five neonatal piglets were studied in a 7 T/20 cm bore magnet. MRI was conducted using a 2.5 cm diameter surface coil placed over the parietal lobes. Four progressively T2*‐weighted images were acquired, allowing the absolute quantitation of R2*. Simultaneous near infrared spectroscopy (NIRS) measurements were made from an area encompassing the MR imaging slice, and allowed the absolute quantitation of [dHb]. The arterial oxygen saturation (SaO2) of the piglet was lowered stepwise by decreasing the fractional inspired oxygen concentration (FiO2), which precipitated a change in [dHb]. NIRS and MRI measurements were made at each FiO2 step. The results demonstrate an extremely strong, linear relationship between R2* as determined by MRI and [dHb], as measured by NIRS. Whereas NIRS can only give us a global measure of [dHb], the results suggest the future use of MRI in producing high resolution relaxation rate maps related to the [dHb] distribution of the brain.

Use of mitochondrial inhibitors to demonstrate that cytochrome oxidase near-infrared spectroscopy can measure mitochondrial dysfunction noninvasively in the brain.

The use of near-infrared spectroscopy to measure noninvasively changes in the redox state of cerebral cytochrome oxidase in vivo is controversial. We therefore tested these measurements using a multiwavelength detector in the neonatal pig brain. Exchange transfusion with perfluorocarbons revealed that the spectrum of cytochrome oxidase in the near-infrared was identical in the neonatal pig, the adult rat, and in the purified enzyme. Under normoxic conditions, the neonatal pig brain contained 15 μmol/L deoxyhemoglobin, 29 μmol/L oxyhemoglobin, and 1.2 μmol/L oxidized cytochrome oxidase. The mitochondrial inhibitor cyanide was used to determine whether redox changes in cytochrome oxidase could be detected in the presence of the larger cerebral hemoglobin concentration. Addition of cyanide induced full reduction of cytochrome oxidase in both blooded and bloodless animals. In the blooded animals, subsequent anoxia caused large changes in hemoglobin oxygenation and concentration but did not affect the cytochrome oxidase near-infrared signal. Simultaneous blood oxygenation level-dependent magnetic resonance imaging measurements showed a good correlation with near-infrared measurements of deoxyhemoglobin concentration. Possible interference in the near-infrared measurements from light scattering changes was discounted by simultaneous measurements of the optical pathlength using the cerebral water absorbance as a standard chromophore. We conclude that, under these conditions, near-infrared spectroscopy can accurately measure changes in the cerebral cytochrome oxidase redox state.

Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia

Measurements of tissue water apparent diffusion coefficient (ADC) performed with diffusion sensitization applied separately along the x, y, and z axes revealed significant diffusion anisotropy in both cerebral white and gray matter in six newborn (< 24 h old) piglets. Mean baseline white matter ADC for a particular region of interest was 125.8% (SD 32.0%; p < .001) greater when the diffusion gradients were applied along the y axis as compared to along the x. For the cortical gray matter region considered, the situation was reversed, the mean ADC value measured along x exceeding that along y by 15.2% (SD 6.1%; p < .01). Forty-three hours subsequent to a transient cerebral hypoxic-ischaemic insult, phosphorous MRS measurements indicated that the animals had suffered severe secondary cerebral energy failure. This was accompanied by a significant (p < .01) decrease in the white matter anisotropy, such that the mean y direction ADC now exceeded that along the x by only 70.9% (SD 29.4%; p < .03). There was no change in the gray matter anisotropy. The average of the ADC values measured in the x, y, and z directions had decreased by 35.3% (SD 18.5%; p < .01) in white matter and 31.4% (SD 21.9%; p < .05) in cortical gray matter. Diffusion anisotropy measurements may provide additional information useful in the characterisation of hypoxic-ischaemic injury in the neonatal brain, and must be considered if tissue water ADC values are to be unambiguously interpreted in this context.