Higher perfusion of rectum carcinoma relative to tumor-free rectal wall: quantification by a new imaging biomarker diffusion-derived vessel density (DDVD).

Background: Diffusion-derived vessel density (DDVD) is a physiological surrogate of the area of micro-vessels per unit tissue area. DDVD is calculated according to: DDVD(b0b5) = Sb0/ROIarea0 - Sb5/ROIarea5, where Sb0 and Sb5 refer to the tissue signal when b is 0 or 5 s/mm2. This study applied DDVD to assess the perfusion of rectal carcinoma (RC). Methods: MRI was performed with a 3.0-T magnet. Diffusion weighted image with b-values of 0, 5 s/mm2 were acquired in 113 patients with non-mucinous RC and 15 patients with mucinous RC. Diffusion-derived vessel density ratio [DDVDr(b0b5)] was DDVD(b0b5) of RC divided by DDVD(b0b5) of tumor-free rectal wall. Results: The median value of the DDVDr(b0b5) for non-mucinous RCs was 1.430, with the majority of RCs showing a higher DDVD than the adjacent tumor-free wall [i.e., with DDVDr(b0b5) >1]. 90.3% (102/113) of non-mucinous RCs were hypervascular, 1.77% (2/113) were iso-vascular, and 7.96% (9/113) were hypovascular. The median value of the DDVDr(b0b5) for mucinous RCs was 1.660. 73.3% (11/15) of mucinous RCs were hypervascular, and 26.7% (4/15) were hypovascular. A trend (P=0.09) was noted that earlier clinical grades non-mucinous RCs had a higher DDVDr(b0b5) than those of the advanced clinical grades (2.245 for grade 0&I, 1.460 for grade II, 1.430 for grade III, 1.130 for grade IV). A non-significant trend was noted with well and moderately differentiated non-mucinous RCs had a higher DDVDr(b0b5)than that of poorly differentiated non-mucinous RCs (median: 1.460 vs. 1.320). A non-significant trend was noted with MRI-detected extramural vascular invasion (mrEMVI) positive non-mucinous RCs had a higher DDVDr(b0b5) than that of mrEMVI negative non-mucinous RCs (1.630 vs. 1.370). Conclusions: DDVD results in this study approximately agree with contrast agent dynamically enhanced CT literature data.

Diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol as a biomarker of placental blood circulation in patients with placenta accreta spectrum disorders: A proof-of-concept study.

OBJECTIVES: Increasing trend of PAS (placenta accreta spectrum disorders) incidence is a major health concern as PAS is associated with high maternal morbidity and mortality during cesarean section. Prenatal identification of PAS is crucial for delivery planning and patients management. This study aims to explore whether diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol differs in PAS from normal placenta. METHODS: We enrolled 86 patients with PAS disorders and 40 pregnant women without PAS disorders. Each patient underwent intravoxel incoherent motion (IVIM) MRI sequence with 11 b-values. Placenta diffusion-derived vessel density (DDVD-b0b50) was the signal difference between b = 0 and b = 50 s/mm2 images. DDVD(b0b50) A/N was calculated as [accreta lesion DDVD(b0b50)]/ [normal placenta DDVD(b0b50)]. The correlation between DDVD and gestational age was explored using Spearman rank correlation. Differences of DDVD(b0b50) A/N in patients with normal placentas and with PAS, and in patients with different subtypes of PAS were explored. RESULTS: DDVD was negatively correlated with gestational age (p = 0.023, r = -0.359) in patients with normal placentas. DDVD(b0b50) A/N was significantly higher in patients with PAS (median:1.16, mean: 1.261) than normal placenta (median:1.02, mean: 1.032, p < 0.001) and especially higher in patients with placenta increta (median:1.14, mean: 1.278) and percreta (median: 1.20, mean: 1.396, p < 0.001). CONCLUSION: As a higher DDVD indicates higher physiological volume of micro-vessels in PAS, this study suggests DDVD can be a potential biomarker to evaluate the placenta perfusion.

East Asians' T-scores for the diagnosis of osteoporosis should be calculated using ethnicity- and gender-specific BMD reference ranges: justifications.

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.

Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences.

For liver intravoxel incoherent motion (IVIM) data acquisition, respiratory-triggering (RT) MRI is commonly used, and there are strong motivations to shorten the scan duration. For the same scan duration, more b values or higher numbers of excitations can be allowed for free-breathing (FB) imaging than for RT. We studied whether FB can be used to replace RT when careful IVIM image acquisition and image processing are conducted. MRI data of 22 healthy participants were acquired using a 3.0 T scanner. Diffusion imaging was based on a single-shot spin-echo-type echo-planar sequence and 16 b values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, and 600 s/mm2 . Each subject attended two scan sessions with an interval of 10-20 days. For each scan session, a subject was scanned twice, first with RT and then with FB. The mean image acquisition time was 5.4 min for FB and 10.8 min for RT. IVIM parameters were calculated with bi-exponential model segmented fitting with a threshold b value of 60 s/mm2 , and fitting started from b = 2 s/mm2 . There was no statistically significant difference between IVIM parameters measured with FB imaging or RT imaging. Perfusion fraction ICC (intraclass correlation coefficient) for FB imaging and RT imaging in the same scan session was 0.824. For perfusion fraction, wSD (within-subject standard deviation), BA (Bland-Altman) difference, BA 95% limit, and ICC were 0.022, 0.0001, -0.0635~0.0637, and 0.687 for FB and 0.031, 0.0122, -0.0723~0.0967, and 0.611 for RT. For Dslow (×10-3  s/mm2 ), wSD, BA difference, BA 95% limit, and ICC were 0.057, 0.0268, -0.1258~0.1793, and 0.471 for FB and 0.073, -0.0078, -0.2170-0.2014, and <0.4 for RT. The Dfast coefficient of variation was 0.20 for FB imaging and 0.28 for RT imaging. All reproducibility indicators slightly favored FB imaging.

Estimations of bone mineral density defined osteoporosis prevalence and cutpoint T-score for defining osteoporosis among older Chinese population: a framework based on relative fragility fracture risks.

This study estimated the bone mineral density (BMD) defined osteoporosis prevalence of Chinese women and Chinese men aged ≥50 years. The estimation was based on the 1994 WHO definition of osteoporosis and two assumptions: (I) fragility fracture (FF) risk among older Chinese is half of that of older US Caucasians; (II) FF risk among older Chinese men is half of that of older Chinese women. In addition, we also consider the FF risk among older Chinese is close to those of American Blacks. We estimated that the osteoporosis prevalence based on lumbar BMD, femoral neck BMD, total hip BMD would be 15.8%, 20.4%, and 15.2% for US Caucasian women, 6.7%, 7.8%, and 7.9% for US black women, 7.5%, 7.5%, and 6.7% for Chinese women, 1.8%, 5.7%, and 3.3% for US black men, and 2.0%, 3.8%, and 3.4% for Chinese men. To satisfy the above estimates of osteoporosis prevalence for the Chinese population, in addition to using a local reference database, we suggest that the T-score cutpoints for defining osteopenia and osteoporosis among older Chinese should be adjusted from the conventional WHO thresholds of -2.5 and -1.0. Our suggested revised cutpoint T-score for defining osteoporosis described in this article will be more in line with the original WHO definition and will allow a more meaningful international comparison of disease burden.

A software program for automated compressive vertebral fracture detection on elderly women's lateral chest radiograph: Ofeye 1.0.

Background: Because osteoporotic vertebral fracture (OVF) on chest radiographs is commonly missed in radiological reports, we aimed to develop a software program which offers automated detection of compressive vertebral fracture (CVF) on lateral chest radiographs, and which emphasizes CVF detection specificity with a low false positivity rate. Methods: For model training, we retrieved 3,991 spine radiograph cases and 1,979 chest radiograph cases from 16 sources, with among them in total 1,404 cases had OVF. For model testing, we retrieved 542 chest radiograph cases and 162 spine radiograph cases from four independent clinics, with among them 215 cases had OVF. All cases were female subjects, and except for 31 training data cases which were spine trauma cases, all the remaining cases were post-menopausal women. Image data included DICOM (Digital Imaging and Communications in Medicine) format, hard film scanned PNG (Portable Network Graphics) format, DICOM exported PNG format, and PACS (Picture Archiving and Communication System) downloaded resolution reduced DICOM format. OVF classification included: minimal and mild grades with <20% or ≥20-25% vertebral height loss respectively, moderate grade with ≥25-40% vertebral height loss, severe grade with ≥40%-2/3 vertebral height loss, and collapsed grade with ≥2/3 vertebral height loss. The CVF detection base model was mainly composed of convolution layers that include convolution kernels of different sizes, pooling layers, up-sampling layers, feature merging layers, and residual modules. When the model loss function could not be further decreased with additional training, the model was considered to be optimal and termed 'base-model 1.0'. A user-friendly interface was also developed, with the synthesized software termed 'Ofeye 1.0'. Results: Counting cases and with minimal and mild OVFs included, base-model 1.0 demonstrated a specificity of 97.1%, a sensitivity of 86%, and an accuracy of 93.9% for the 704 testing cases. In total, 33 OVFs in 30 cases had a false negative reading, which constituted a false negative rate of 14.0% (30/215) by counting all OVF cases. Eighteen OVFs in 15 cases had OVFs of ≥ moderate grades missed, which constituted a false negative rate of 7.0% (15/215, i.e., sensitivity 93%) if only counting cases with ≥ moderate grade OVFs missed. False positive reading was recorded in 13 vertebrae in 13 cases (one vertebra in each case), which constituted a false positivity rate of 2.7% (13/489). These vertebrae with false positivity labeling could be readily differentiated from a true OVF by a human reader. The software Ofeye 1.0 allows 'batch processing', for example, 100 radiographs can be processed in a single operation. This software can be integrated into hospital PACS, or installed in a standalone personal computer. Conclusions: A user-friendly software program was developed for CVF detection on elderly women's lateral chest radiographs. It has an overall low false positivity rate, and for moderate and severe CVFs an acceptably low false negativity rate. The integration of this software into radiological practice is expected to improve osteoporosis management for elderly women.

Bi-exponential fitting excluding b=0 data improves the scan-rescan stability of liver IVIM parameter measures and particularly so for the perfusion fraction.

Background: A prerequisite to translating intravoxel incoherent motion (IVIM) imaging into meaningful clinical applications is sufficient scan-rescan reproducibility. This study aims to confirm the hypothesis that IVIM data fitting by not using b=0 images will improve the stability of liver IVIM measurement. Methods: Healthy volunteers' liver IVIM images were prospectively acquired using a 1.5-T magnet or a 3.0 T with 16 b-values. Repeatability study subjects were scanned twice during the same session, resulted in 35 paired scans for 35 subjects (11 men, mean age: 41.82 years, range: 32-60 years; 24 women, mean age: 42.67 years, range: 20-71 years). IVIM analysis was performed with full-fitting and segmented-fitting with a threshold b-value of 60 s/mm2, and fitting started from b=0 s/mm2 or from b=2 s/mm2. Reproducibility study subjects were scanned and then rescanned with an interval of 5-18 days, resulted in 20 paired scans for 11 subjects (4 men, mean age: 26.25 years, range: 25-27 years; 7 women, mean age: 25.57 years, range: 24-27 years). IVIM analysis was performed with segmented-fitting with a threshold b-value of 50 s/mm2, and fitting started from b=0 s/mm2 or from b=3 s/mm2. Results: Fitting without b=0 data generally improved the repeatability and reproducibility for both PF and Dslow, and particularly so for PF. For with b=0 data segmented fitting repeatability, PF had within-subject standard deviation of 0.019, bland-Atman 75% agreement limit of -31.52% to 28.35%, and ICC of 0.647, while these values were 0.009, -20.78% to 16.86%, and 0.837 for without b=0 analysis. Though the repeatability and reproducibility for Dfast generally also improved, they remained suboptimal. Measurement stability was better for repeatability than for reproducibility. Conclusions: Scan-rescan repeatability and reproducibility of liver IVIM parameters can be improved by fitting without b=0 data, which is particularly so for PF.

Spleen in viral Hepatitis-B liver fibrosis patients may have a reduced level of per unit micro-circulation: non-invasive diffusion MRI evidence with a surrogate marker.

Spleen micro-perfusion level can be evaluated by DDVD (diffusion derived vessel density): DDVD (unit: au/pixel) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the spleen signal when b is 0 or 2 (s/mm2) and ROI is 'region-of-interest'. This study investigated whether spleen DDVD is altered in patients with viral hepatitis-b (VHB) liver fibrosis. Three datasets were retrospectively analysed. Shenzhen data-1 had 25 healthy volunteers and 15 VHB liver fibrosis patients. Changsha data had 24 healthy volunteers and 31 patients with VHB liver fibrosis. Shenzhen data-2 had 67 healthy volunteers. Shenzhen data-2 were measured by reader-1. Shenzhen data-1 were measured by reader-1 and reader-2. For Changsha data, reader-1 measured all subjects, while Reader-2 measured a random selection of 10 healthy volunteers and two patients from each liver fibrosis grade (total=8). Shenzhen data-2 showed in healthy volunteers there was no age-dependent change of spleen DDVD during 20 ∼71 years old, and women had higher spleen DDVD values than those of men's (16.17±7.34 vs. 12.88±5.91, p=0.04). Changsha data by reader-1 showed patients with liver fibrosis had lower spleen DDVD values than those of healthy volunteers (median=16.24 vs. 23.54, p=0.0031). Results of reader-2 showed the same trend (median=11.64 vs. 23.33, p=0.0165). Shenzhen data-1 measured by reader-1 showed medians of spleen DDVD for patients and volunteers were 8.535 and 12.33 respectively; and those measured by reader-2 were 13.89 and 14.31 respectively. We conclude that diffusion MRI shows spleen DDVD, i.e., micro-circulation per volume tissue, is decreased in VHB liver fibrosis patients.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.

Diffusion-weighted MRI of the liver: challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion.

Diffusion-weighted imaging (DWI) is sensitive to the mobility of water molecule at cellular and macromolecular level, much smaller than the spatial resolution of the images. It is commonly based on single shot echo-planar imaging sequence with the addition of motion-probing gradient pulses and fat suppression. DWI is increasingly incorporated into routine body magnetic resonance imaging protocols. However, the liver is particularly affected by physiological motions such as respiration; the left liver is also affected by cardiac motion artifacts and susceptibility artefact due to contents in the stomach. Intravoxel incoherent motion (IVIM) DWI data analysis requires high-quality data acquisition using multiple b-values and confidence in the measurements at low b-values. This article reviews the technical developments of DWI and its applications in the liver. Challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion are discussed. Currently, acquisition protocols vary between research groups; patient preparation and data post-processing are not standardized. Increased standardization, both in data acquisition and in image analysis, is imperative so to allow generation of reliable DW-MRI biomarker measures that are broadly applicable.