Human trophectoderm becomes multi-layered by internalization at the polar region.

To implant in the uterus, mammalian embryos form blastocysts comprising trophectoderm (TE) surrounding an inner cell mass (ICM), confined to the polar region by the expanding blastocoel. The mode of implantation varies between species. Murine embryos maintain a single layered TE until they implant in the characteristic thick deciduum, whereas human blastocysts attach via polar TE directly to the uterine wall. Using immunofluorescence (IF) of rapidly isolated ICMs, blockade of RNA and protein synthesis in whole embryos, or 3D visualization of immunostained embryos, we provide evidence of multi-layering in human polar TE before implantation. This may be required for rapid uterine invasion to secure the developing human embryo and initiate formation of the placenta. Using sequential fluorescent labeling, we demonstrate that the majority of inner TE in human blastocysts arises from existing outer cells, with no evidence of conversion from the ICM in the context of the intact embryo.

Can species guilds act as hubs for energy transfer in macrophyte meadows of Amazonian floodplain lakes?

Aquatic macrophytes are the main autochthonous component of primary production in the Amazon Basin. Floating meadows of these plants support habitats with highly diverse animal communities. Fishes inhabiting these habitats have been assumed to use a broad range of food items and compose a particular food web. We employed carbon (δ13C) and nitrogen (δ15N) stable isotope analysis to draw the trophic structure of these habitats and to trace the energy flow by its trophic levels. Fishes and other animals from 18 independent macrophyte meadows of a floodplain lake of the Solimões River (Amazonia, Brazil) were analyzed. The food web of macrophyte meadows consists of four trophic levels above autotrophic sources. In general, primary consumers exhibited a broader range of food sources than the upper trophic levels. Some fish species depended on a large number of food sources and at the same time are consumed by several predators. The energy transfer from one trophic level to the next was then mainly accomplished by these species concentrating a high-energy flux and acting as hubs in the food web. The broad range of δ13C values observed indicates that the organisms living in the macrophyte meadows utilize a great diversity of autotrophic sources.

Assessment of 18F-DCFPyL PSMA PET/CT and PET/MR quantitative parameters for reference standard organs: Inter-reader, inter-modality, and inter-patient variability.

Prostate specific membrane antigen (PSMA)-based radiotracers have shown promise for prostate cancer assessment. Evaluation of quantitative variability and establishment of reference standards are important for optimal clinical and research utility. This work evaluates the variability of PSMA-based [18F]DCFPyL (PyL) PET quantitative reference standards. Consecutive eligible patients with biochemically recurrent prostate cancer were recruited for study participation from August 2016-October 2017. After PyL tracer injection, whole body PET/CT (wbPET/CT) was obtained with subsequent whole body PET/MR (wbPET/MR). Two readers independently created regions of interest (ROIs) including a 40% standardized uptake value (SUV) threshold ROI of the whole right parotid gland and separate spherical ROIs in the superior, mid, and inferior gland. Additional liver (right lobe) and blood pool spherical ROIs were defined. Bland-Altman analysis, including limits of agreement (LOA), as well as interquartile range (IQR) and coefficient of variance (CoV) was used. Twelve patients with prostate cancer were recruited (mean age, 61.8 yrs; range 54-72 years). One patient did not have wbPET/MR and was excluded. There was minimal inter-reader SUVmean variability (bias±LOA) for blood pool (-0.13±0.42; 0.01±0.41), liver (-0.55±0.82; -0.22±1.3), or whole parotid gland (-0.05±0.31; 0.08±0.24) for wbPET/CT and wbPET/MR, respectively. Greater inter-reader variability for the 1-cm parotid gland ROIs was present, for both wbPET/CT and wbPET/MR. Comparing wbPET/CT to the subsequently acquired wbPET/MR, blood pool had a slight decrease in SUVmean. The liver as well as parotid gland showed a slight increase in activity although the absolute bias only ranged from 0.45-1.28. The magnitude of inter-subject variability was higher for the parotid gland regardless of modality or reader. In conclusion, liver, blood pool, and whole parotid gland quantitation show promise as reliable reference normal organs for clinical/research PET applications. Variability with 1-cm parotid ROIs may limit its use.

Automated MR Image Prescription of the Liver Using Deep Learning: Development, Evaluation, and Prospective Implementation.

BACKGROUND: There is an unmet need for fully automated image prescription of the liver to enable efficient, reproducible MRI. PURPOSE: To develop and evaluate artificial intelligence (AI)-based liver image prescription. STUDY TYPE: Prospective. POPULATION: A total of 570 female/469 male patients (age: 56 ± 17 years) with 72%/8%/20% assigned randomly for training/validation/testing; two female/four male healthy volunteers (age: 31 ± 6 years). FIELD STRENGTH/SEQUENCE: 1.5 T, 3.0 T; spin echo, gradient echo, bSSFP. ASSESSMENT: A total of 1039 three-plane localizer acquisitions (26,929 slices) from consecutive clinical liver MRI examinations were retrieved retrospectively and annotated by six radiologists. The localizer images and manual annotations were used to train an object-detection convolutional neural network (YOLOv3) to detect multiple object classes (liver, torso, and arms) across localizer image orientations and to output corresponding 2D bounding boxes. Whole-liver image prescription in standard orientations was obtained based on these bounding boxes. 2D detection performance was evaluated on test datasets by calculating intersection over union (IoU) between manual and automated labeling. 3D prescription accuracy was calculated by measuring the boundary mismatch in each dimension and percentage of manual volume covered by AI prescription. The automated prescription was implemented on a 3 T MR system and evaluated prospectively on healthy volunteers. STATISTICAL TESTS: Paired t-tests (threshold = 0.05) were conducted to evaluate significance of performance difference between trained networks. RESULTS: In 208 testing datasets, the proposed method with full network had excellent agreement with manual annotations, with median IoU > 0.91 (interquartile range < 0.09) across all seven classes. The automated 3D prescription was accurate, with shifts <2.3 cm in superior/inferior dimension for 3D axial prescription for 99.5% of test datasets, comparable to radiologists' interreader reproducibility. The full network had significantly superior performance than the tiny network for 3D axial prescription in patients. Automated prescription performed well across single-shot fast spin-echo, gradient-echo, and balanced steady-state free-precession sequences in the prospective study. DATA CONCLUSION: AI-based automated liver image prescription demonstrated promising performance across the patients, pathologies, and field strengths studied. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 1.

Household and area determinants of emergency department attendance and hospitalisation in people with multimorbidity: a systematic review.

OBJECTIVES: Multimorbidity is one of the greatest challenges facing healthcare internationally. Emergency department (ED) attendance and hospitalisation rates are higher in people with multimorbidity, but most research focuses on associations with individual characteristics, ignoring household or area mediators of service use. DESIGN: Systematic review reported using the synthesis without meta-analysis framework. DATA SOURCES: Twelve electronic databases (1 January 2000-21 September 2021): MEDLINE/OVID, Embase, Global Health, PsycINFO, ASSIA, CAB Abstracts, Science Citation Index Expanded/ISI Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts, the Cochrane Library, and OpenGrey. ELIGIBILITY CRITERIA: Adults aged ≥16 years, with multimorbidity. Exposure(s) were household and/or area determinants of health. Outcomes were ED attendance and/or hospitalisation. The literature search was limited to publications in English. DATA EXTRACTION AND SYNTHESIS: Independent double screening of titles and abstracts to select relevant full-text studies. Methodological quality was assessed using an adaptation of the Newcastle-Ottawa Quality Assessment Scale tool. Given high study heterogeneity, narrative synthesis was performed. RESULTS: After deduplication, 10 721 titles and abstracts were screened, and 142 full-text articles were reviewed, of which 10 were eligible for inclusion. In people with multimorbidity, household food insecurity was associated with hospitalisation (OR 1.58 (95% CI 1.06 to 2.36) in concordant multimorbidity). People with multimorbidity living in the most versus least deprived areas attended ED more frequently (8.9% (95% CI 8.6 to 9.1) in most versus 6.3% (95% CI 6.1 to 6.6) in least), had higher rates of hospitalisation (26% in most versus 22% in least), and higher probability of hospitalisation (6.4% (95% CI 5.8 to 7.2) in most versus 4.2% (95% CI 3.8 to 4.7) in least). There was non-conclusive evidence that household income is associated with ED attendance and hospitalisation. No statistically significant relationships were found between marital status, living with others with multimorbidity, or rurality with ED attendance or hospitalisation. CONCLUSIONS: There is some evidence that household and area contexts mediate associations of multimorbidity with ED attendance and hospitalisation, but firm conclusions are constrained by the small number of studies published and study design heterogeneity. Further research is required on large population samples using robust analytical methods. PROSPERO REGISTRATION NUMBER: CRD42021283515.

Reduced field-of-view and multi-shot DWI acquisition techniques: Prospective evaluation of image quality and distortion reduction in prostate cancer imaging.

OBJECTIVES: To prospectively compare image quality and apparent diffusion coefficient (ADC) quantification for reduced field-of-view (rFOV)- and multi-shot echo-planar imaging (msEPI)-based diffusion weighted imaging (DWI), using single-shot echo-planar-imaging (ssEPI) DWI as the reference. METHODS: Under IRB approval and after informed consent, msEPI, rFOV, and ssEPI DWI acquisitions were prospectively added to clinical prostate MRI exams at 3.0 T. Image distortion was quantitatively evaluated by root-mean-squared displacement (dr.m.s.). Histogram-based quantitative ADC parameters were compared in a sub-set of patients for proven sites of prostate cancer and matched non-cancerous prostate. Three radiologists also independently evaluated the DWI sequences for subjective image quality and distortion/artifact on a 5-point Likert scale. RESULTS: Twenty-five patients were included (15 with proven sites of cancer). Average dr.m.s. demonstrated a small but statistically significant reduction in distortion for both rFOV and msEPI relative to ssEPI. Quantitative ADC parameters for prostate tumors demonstrated no significant difference across the 3 DWI acquisitions and each acquisition demonstrated a statistically significant decrease in mean ADC for tumor compared to normal prostate. Qualitative reader assessment demonstrated favorable image quality for rFOV and msEPI, more notable for msEPI. CONCLUSIONS: rFOV and msEPI DWI techniques achieved reduction in image distortion, improvement in image quality, and maintained reproducible ADC quantification compared to the standard ssEPI.

Evaluation of Guideline Adherence and Subsequent Follow-Up Outcomes for Incidental Thyroid Nodules Detected in Hybrid Academic-Community Practice.

OBJECTIVE: Incidental thyroid nodules (ITNs) are common, and variability regarding follow-up and recommendation practices exist. The study purpose was to determine adherence to the American College of Radiology (ACR) ITN criteria and analyze recommendation outcomes. METHODS: ITNs listed in the impression section on computed tomography, magnetic resonance imaging, and positron emission tomography studies over a 6-month period were included. Report recommendations were compared with ACR white paper criteria for adherence (concordant recommendation) or nonadherence (discordant recommendation). Reader characteristics, further ITN workup, and pathology were recorded. A P value less than 0.05 was used for significance. RESULTS: Three hundred fifty patients (mean age, 64.6 years) were included with a median ITN size of 18-mm. Most nodules (289/350) were reported on computed tomography and were identified for follow-up due to size (235/350). Only 39 of 350 reports (11.1%) did not follow ACR recommendations. Patient age was significantly related to recommendation adherence ( P < 0.05) as opposed to radiologist practice type (ie, community-based or academic) which was not. Nonadherence most often involved recommending ultrasound follow-up for nonactionable small ITNs. The rate of fine-needle aspiration biopsy from concordant ITNs was significantly higher than discordant ITNs ( P < 0.05). Six patients, all with concordant recommendations, had malignant final pathology results. CONCLUSION: Recommendation adherence to the ACR ITN criteria was high, approaching 90%. Nonadherence was mostly due to recommending thyroid ultrasound when not indicated and was correlated with a younger patient age. The rate of fine-needle aspiration biopsy stemming from nonindicated ultrasounds was significantly lower and did not result in the diagnosis of any malignancies.

Ultrasound-guided biopsy of challenging abdominopelvic targets.

Percutaneous ultrasound-guided biopsies have become the standard of practice for tissue diagnosis in the abdomen and pelvis for many sites including liver, kidney, abdominal wall, and peripheral nodal stations. Additional targets may appear difficult or impossible to safely biopsy by ultrasound due to interposed bowel loops/vasculature, deep positioning, association with the bowel, or concern for poor visibility; however, by optimizing technique, it is often possible to safely and efficiently use real-time ultrasound guidance for sampling targets that normally would be considered only appropriate for CT guided or surgical/endoscopic biopsy.

Evaluating suspected small bowel obstruction with the water-soluble contrast challenge.

With optimized technique, the water-soluble contrast challenge is effective at triaging patients for operative vs non-operative management of suspected small bowel obstruction. Standardized study structure and interpretation guidelines aid in clinical efficacy and ease of use. Many tips and tricks exist regarding technique and interpretation, and their understanding may assist the interpreting radiologist. In the future, a CT-based water-soluble contrast challenge, utilizing oral contrast given as part of the initial CT examination, might allow for a more streamlined algorithm and provide more rapid results.

Water-Soluble Contrast Challenge for Suspected Small-Bowel Obstruction: Technical Success Rate, Accuracy, and Clinical Outcomes.

Among 109 iohexol-based water-soluble contrast (WSC) challenges performed for suspected small-bowel obstruction, 105 were technically adequate. Among technically adequate studies, colonic contrast (i.e., successful challenge) was seen on 66 abdominal radiographs obtained 8 hours after WSC challenge and 86 abdominal radiographs obtained 24 hours after WSC challenge. Fourteen patients underwent operative management, and 91 underwent nonoperative management (NOM). Successful challenge had a sensitivity of 91.2%, specificity of 78.5%, PPV of 96.5%, NPV of 57.8%, and odds ratio of 38.0 (95% CI, 8.7-165.2) for NOM. Three of 86 patients with successful challenge underwent operative management.

Effect of noise and estimator type on bias for analysis of liver proton density fat fraction.

PURPOSE: Proton-density fat-fraction (PDFF) is typically measured from PDFF maps by calculating the mean PDFF value within a region of interest (ROI). However, the mean estimator has been shown to result in bias when signal-to-noise ratio (SNR) is low, resulting from a skewed distribution of PDFF noise statistics. Thus, the purpose of this work was to determine the relative performance of three estimation methods (mean, median, maximum likelihood estimators (MLE)) for analysis of liver PDFF maps. METHODS: Observational study of adult patients (n = 56) undergoing abdominal MRI. Both 2D-sequential CSE-MRI ('low-SNR') and 3D CSE-MRI ('high-SNR') acquisitions were obtained. Single-voxel MRS formed the independent reference measurement of hepatic PDFF. Intra-class correlation was tested on a subset of 'low-SNR' acquisitions. ROIs were semi-automatically co-registered across all acquisitions. Bland-Altman analysis and intra-class correlation coefficients were used for statistical analysis. A p-value of <0.05 was considered significant. RESULTS: For in vivo low-SNR acquisitions, the mean estimator had a larger error than either the median or MLE values (bias ~ -1% absolute PDFF). The intra-class correlation coefficient was significantly greater for median and maximum likelihood estimators (0.992 and 0.993, respectively) compared to the mean estimator (0.973). CONCLUSION: Alternative ROI analysis strategies, such as MLE or median estimators, are useful to avoid SNR-related PDFF bias. Median may be the most clinically practical strategy given its ease of calculation.

Removing rician bias in diffusional kurtosis of the prostate using real-data reconstruction.

PURPOSE: To compare prostate diffusional kurtosis imaging (DKI) metrics generated using phase-corrected real data with those generated using magnitude data with and without noise compensation (NC). METHODS: Diffusion-weighted images were acquired at 3T in 16 prostate cancer patients, measuring 6 b-values (0-1500 s/mm2 ), each acquired with 6 signal averages along 3 diffusion directions, with noise-only images acquired to allow NC. In addition to conventional magnitude averaging, phase-corrected real data were averaged in an attempt to reduce rician noise-bias, with a range of phase-correction low-pass filter (LPF) sizes (8-128 pixels) tested. Each method was also tested using simulations. Pixelwise maps of apparent diffusion (D) and apparent kurtosis (K) were calculated for magnitude data with and without NC and phase-corrected real data. Average values were compared in tumor, normal transition zone (NTZ), and normal peripheral zone (NPZ). RESULTS: Simulations indicated LPF size can strongly affect K metrics, where 64-pixel LPFs produced accurate metrics. Relative to metrics estimated from magnitude data without NC, median NC K were lower (P < 0.0001) by 6/11/8% in tumor/NPZ/NTZ, 64-LPF real-data K were lower (P < 0.0001) by 4/10/7%, respectively. CONCLUSION: Compared with magnitude data with NC, phase-corrected real data can produce similar K, although the choice of phase-correction LPF should be chosen carefully.

Repeatability of diffusion-weighted MRI of the prostate using whole lesion ADC values, skew and histogram analysis.

PURPOSE: To investigate the repeatability of diffusion-weighted imaging parameter including ADC-derived histogram values in prostate cancer. METHODS: 10 patients with prostate cancer were prospectively recruited to a retest cohort. 3 T diffusion-weighted MRI of the prostate was acquired consecutively with patient getting off the scanner between studies. Prostatectomy-histopathology defined tumour regions-of-interest were outlined on ADC maps and diffusion-weighted metrics including histograms were calculated. The coefficient of reproducibility (CoR) and Bland-Altman plots were used to assess repeatability. RESULTS: 10th centile, 90th centile, and median ADC showed good repeatability with mean difference ranging from -0.005 to -0.025 × 103 mm2s-1, and CoR ranging from 0.271-0.294 × 103 mm2s-1 of scan 1 mean). Two measures of heterogeneity and simplified texture, IQR and mean local range, had only moderate repeatability. IQR had a mean difference of -0.032 × 103 mm2s-1 between scans with CoR 0.181 × 103 mm2s-1 (56% of scan 1 mean). Mean local range had a mean difference -0.008 × 103 mm2s-1 between scans (37% of scan 1 mean). Bland-Altman plots showed good repeatability for test and re-test analysis for median, percentile and mean range values. All ADC values had good reliability regardless of whether the tumour border was included in quantitative analysis. ADC histogram skew had poor repeatability, CoR 0.78 × 103 mm2s-1 (373% of scan 1 mean). CONCLUSION: 10th and 90th centile ADC demonstrated sufficient repeatability for clinical use. However, more advanced measures of heterogeneity such as histogram skew, IQR, or mean local range may be limited by their repeatability.

Barriers to compliance with emergency department discharge instructions: lessons learned from patients' perspectives.

The objective of this study is to understand patients' perspectives about system-based barriers that may influence decision-making regarding following discharge instructions. In this qualitative study, subjects were interviewed by phone 1-4 weeks following being discharged to home from the emergency department (ED). We used a semi-structured interview guide to ask a series of open-ended questions about subjects' recent ED visit and subsequent course, including discharge instructions, whether or not they complied with those instructions, and reasoning behind their decisions to follow-up or not. All interviews were recorded and transcribed to identify themes among the transcripts, which were analyzed to identify barriers to compliance. While the majority of those interviewed expressed no specific concerns or challenges, four system-based themes did emerge regarding patient attitudes toward and experiences with discharge instructions. They were: (1) failure to ensure clarity about diagnosis at the time of discharge from the ED, (2) failure to identify patients' feelings of hopelessness regarding the utility of follow-up, (3) difficulty in scheduling follow-up appointments, and (4) the importance of a clear discharge process. This study finds several system-based barriers might influence compliance. The four identified themes suggest a recurring cycle of visiting the ED, being discharged to primary care or specialists, and ultimately returning to the ED. We propose that systems-based interventions may help to break this cycle.

Opportunistic Screening for Hereditary Hemochromatosis With Unenhanced CT: Determination of an Optimal Liver Attenuation Threshold.

OBJECTIVE: The purpose of this study was to assess whether a specific liver attenuation threshold for unenhanced CT allows both sensitive opportunistic detection of unsuspected hereditary hemochromatosis and low overall screening test-positive rates. MATERIALS AND METHODS: We used a standard ROI placement method on unenhanced CT studies of 3357 consecutive adults (mean age, 57.0 years) with no symptoms of liver disease who underwent colorectal screening. Hepatic attenuation (in HU) was measured to assess test-positive rates at various liver attenuation thresholds. To assess sensitivity, unenhanced hepatic CT attenuation was also measured in 12 patients with hereditary hemochromatosis (mean age, 48.3 years), who were homozygous for the HFE C282Y mutation. All scans were obtained at 120 kV. Serum ferritin levels were recorded for the hereditary hemochromatosis cohort. RESULTS: Mean liver attenuation ± SD among screened adults was 59.4 ± 12.7 HU, compared with 78.7 ± 13.1 HU (range, 59-105 HU) in the hereditary hemochromatosis cohort (p < 0.001). Screening test-positive rates were 30.6% (n = 1028) at 65 HU, 8.2% (n = 275) at 70 HU, 1.2% (n = 39) at 75 HU, and 0.2% (n = 7) at 80 HU. Corresponding sensitivities for hereditary hemochromatosis at these thresholds were 83.3% (10/12) at 65, 70, and 75 HU; and 50.0% (6/12) at 80 HU. Serum ferritin levels were elevated in all patients with hereditary hemochromatosis (mean, 1678 ng/mL; range, 477-3991 ng/mL). CONCLUSION: An unenhanced CT liver attenuation threshold of 75 HU was sensitive (83.3%) for hereditary hemochromatosis while maintaining an acceptably low screening test-positive rate (1.2%). An unexplained liver attenuation of 75 HU or more on unenhanced CT should trigger appropriate laboratory investigation for iron overload; early intervention with phlebotomy can limit or prevent organ damage in patients with hemochromatosis.

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population.

OBJECTIVE: To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population. METHODS: Thirty-patients were imaged at 3 T including DKI (Kapp and Dapp) with b-values 150/450/800/1150/1500 s/mm2 and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics. RESULTS: Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and Dapp were significantly lower and the Kapp and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and Dapp and higher Kapp and MTR compared to normal PZ. MTR showed a moderate correlation to Kapp (r = 0.570) and Dapp (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825). CONCLUSION: ADC, Dapp, Kapp and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease. KEY POINTS: • MTR was significantly higher in PZ and TZ tumours versus normal tissue • K app was significantly lower and D app higher for PZ and TZ tumours • There was no incremental value for DKI/MTI over mono-exponential ADC parameters • No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease • Divergent MTR/DKI values in TZ tumours suggests they offer different functional information.

Evaluating Prostate Cancer Using Fractional Tissue Composition of Radical Prostatectomy Specimens and Pre-Operative Diffusional Kurtosis Magnetic Resonance Imaging.

BACKGROUND: Evaluating tissue heterogeneity using non-invasive imaging could potentially improve prostate cancer assessment and treatment. METHODS: 20 patients with intermediate/high-risk prostate cancer underwent diffusion kurtosis imaging, including calculation of apparent diffusion (Dapp) and kurtosis (Kapp), prior to radical prostatectomy. Whole-mount tissue composition was quantified into: cellularity, luminal space, and fibromuscular stroma. Peripheral zone tumors were subdivided according to Gleason score. RESULTS: Peripheral zone tumors had increased cellularity (p<0.0001), decreased fibromuscular stroma (p<0.05) and decreased luminal space (p<0.0001). Gleason score ≥4+3 tumors had significantly increased cellularity and decreased fibromuscular stroma compared to Gleason score ≤3+4 (p<0.05). In tumors, there was a significant positive correlation between median Kapp and cellularity (ρ = 0.50; p<0.05), and a negative correlation with fibromuscular stroma (ρ = -0.45; p<0.05). In normal tissue, median Dapp had a significant positive correlation with luminal space (ρ = 0.65; p<0.05) and a negative correlation with cellularity (ρ = -0.49; p<0.05). Median Kapp and Dapp varied significantly between tumor and normal tissue (p<0.0001), but only median Kapp was significantly different between Gleason score ≥4+3 and ≤3+4 (p<0.05). CONCLUSIONS: Peripheral zone tumors have increased cellular heterogeneity which is reflected in mean Kapp, while normal prostate has a more homogeneous luminal space and cellularity better represented by Dapp.

Single breath counting for the evaluation of pediatric respiratory function: derivation of a "normogram".

Single breath counting (SBC) is the measurement of how far an individual can count in cadence with a metronome set at 2 beats per second in a normal speaking voice following a maximal effort inhalation. Previous work has demonstrated that it correlates well with standard measures of pulmonary function. The objective of this study is to derive a "normogram" of healthy children showing the expected SBC value as a function of easily measured physiologic parameters (age, gender, height, and weight). This was a prospective observational study of a convenience sample of healthy children presenting for well-child checks or non-respiratory complaints at a large tertiary care center. Correlation was determined by the Pearson's product correlation coefficient (r) and r (2) determined as a measure of shared variance. Multiple regression analysis was performed on demographic data to determine a best linear fit with calculation of the coefficient of determination (R (2)). A total of 105 children served as the basis for analysis; 54 (51.4 %) were male and average age was 9.7 (median 10, range 3-15) years. For both males and females, height correlated most strongly with SBC score (r = 0.730 and 0.725, respectively). In both genders, height alone accounted for more than 50 % of the observed variance in the results (r (2) = 0.533 and 0.526, respectively). Breath counting, an easy to perform test that appears to correlate well with standard measures of pulmonary function and shows promise for measuring asthma severity in children. We present an equation for predicting normal results (a "normogram").

Ratio of Tumor to Normal Prostate Tissue Apparent Diffusion Coefficient as a Method for Quantifying DWI of the Prostate.

OBJECTIVE: The purpose of this study was to investigate the ability of the apparent diffusion coefficient (ADC) ratio of tumor to normal prostate tissue to overcome inherent variability based on choice of b values, with whole-mount histopathologic analysis as the reference standard for tumor identification. MATERIALS AND METHODS: Thirty-nine patients with prostate cancer underwent 3-T MRI, including DWI with b values of 0, 150, 750, and 1000 s/mm(2). ADC maps were derived from four b value combinations. Histologically derived ROIs were defined for prostate tumor and benign prostate tissue to generate a ratio. The concordance correlation coefficient was used to evaluate agreement and reproducibility at different b values. Bland-Altman plots were used to evaluate the pattern of relative measurement difference between b value combinations. The relationship between ADC values and Gleason score was tested by Spearman rank correlation. RESULTS: ADC values varied depending on the b value combination selected. The concordance correlation coefficient was higher for ADC ratios (0.883; 95% CI, 0.816-0.927) compared with absolute ADC values for normal tissue (0.873; 95% CI, 0.799-0.921) and tumor (0.792; 95% CI, 0.688-0.864). The ADC ratio concordance correlation coefficient for transition zone tumors was considerably higher than that for the peripheral zone in all cases. Bland-Altman analysis showed higher variation for ADC maps incorporating a b value of zero for both ratio and absolute values. There was a stronger inverse relationship to Gleason score for ADC ratios (rho, -0.354 to -0.456) compared with absolute ADC values (rho, -0.117 to -0.379). CONCLUSION: The use of a simple ratio of prostate tumor ADC to normal tissue ADC improved the concordance between different b value combinations and could provide a more robust means of assessing restricted diffusion in the prostate.