Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

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.

An Ultralight Capillary-Driven Heat Pipe.

Capillary-driven heat pipes are an effective thermal solution for compacting electronic cooling systems. We advance such a heat pipe thermal solution with ultralightweighting for mobile applications. In our advancement, the envelope that encapsulates the phase-change process of a working fluid is fabricated via electroless plating being ∼40 µm thick. Furthermore, the wick structure that transports condensate to a heat source via capillarity is also electroless-plated onto the envelope's inner surfaces, creating a 100-µm-thick, microporous layer. This wick structure is sequentially superhydrophilized by blackening that forms a nanotexture on the microporous wick layer. An effective density of our prototype ultralight heat pipes (uHPs), as a measure of lightweighting, indicates, on average, a remarkable 73% weight reduction of commercial counterparts with sintered copper powder wick in similar exterior dimensions (e.g., ∼2.7 g, compared to ∼10.0 g) while providing equivalent heat spreading. Furthermore, the uHP operates at a 25% lower evaporator temperature, due to additional heat rejection to the surroundings through the ultrathin-walled envelope and wick.

Radiographic Diagnosis of Osteoporotic Vertebral Fracture in Older Women and Men Based on Statistical Probability.

A radiographic gold standard to distinguish osteoporotic vertebral fractures (VFs) from nonosteoporotic VFs does not exist. Radiographic fracture-shaped vertebral deformity (FSVD) is common among young populations with normal bone strength. FSVD in an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely associated with compromised bone strength. For more severe grade deformities or when a vertebra is collapsed, experienced readers can make an osteoporotic VF diagnosis with a high degree of certainty. In milder cases, radiographic osteoporotic VF is often diagnosed based on a high probability rather than an absolute diagnosis. For older women, three nonadjacent minimal grade OLVFs (< 20% height loss), one minimal grade OLVF and one mild OLVF (≥ 20∼25% height loss), or one OLVF with ≥ 25% height loss meets the diagnosis of osteoporosis. For older men, a single OLVF with ≥ 33 to 40% height loss is insufficient to suggest the patient has osteoporosis.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older Chinese men can be the same as that of older Chinese women, both much lower than the value for Caucasians.

For older Caucasian women and men, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) threshold for classifying osteoporosis is 80 mg/ml. It was recently proposed that, for older East Asian women, the QCT LS BMD value equivalent to the Caucasian women's threshold of 80 mg/mL is about 45∼50 mg/ml. For a data of 328 cases of Chinese men (age: 73.6 ± 4.4 years) who had QCT LS BMD and DXA LS BMD at the same time and with the DXA BMD value of ≤ 0.613 g/cm2 to classify osteoporosis, the corresponding QCT LS BMD threshold is 53 mg/ml. Osteoporotic-like vertebral fracture sum score (OLVFss) ≤ -2.5 has been proposed to diagnose osteoporosis. For 316 cases of Chinese men (age:73.7±4.5 years), OLVFss ≤ -2.5 defines an osteoporosis prevalence of 4.4%; to achieve this osteoporosis prevalence, the corresponding QCT LS BMD value is < 47.5 mg/ml. In the China Action on Spine and Hip Status study, a Genant grades 2/3 radiographic 'osteoporotic vertebral fracture' prevalence was 2.84% for Chinese men (total n = 1267, age: 62.77 ± 9.20 years); to achieve this osteoporosis prevalence, the corresponding BMD value was < 42.5 mg/ml. In a study of 357 Beijing older men, according to the clinical fragility fracture prevalence and femoral neck DXA T-score, the QCT LS BMD value to classify osteoporosis was between 39.45 mg/ml and 51.38 mg/ml. For older Chinese men (≥ 50 years), we recommend the cutpoint for the QCT LS BMD definition of osteoporosis to be 45∼50 mg/ml which is the same as the value for Chinese women.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older East Asian women should be lower than the value for Caucasians.

For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.

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.

The observation that older men suffer from hip fracture at DXA T-scores higher than older women and a proposal of a new low BMD category, osteofrailia, for predicting fracture risk in older men.

The clinical significance of osteoporosis lies in the occurrence of fragility fractures (FFx), and the most relevant fracture site is the hip. The T-score is defined as follows: (BMDpatient-BMDyoung adult mean)/SDyoung adult population, where BMD is bone mineral density and SD is the standard deviation. When the femoral neck (FN) is measured in adult Caucasian women, a cutpoint value of patient BMD of 2.5 SD below the young adult mean BMD results in a prevalence the same as the lifetime risk of hip FFx for Caucasian women. The FN T-score criterion for classifying osteoporosis in older Caucasian men has been provisionally recommended to be - 2.5, but debates remain. Based on a systematic literature review, we noted that older men suffer from hip FFx at a FN T-score approximately 0.5-0.6 higher than older women. While the mean hip FFx FN T-score of around - 2.9 for women lies below - 2.5, the mean hip FF FN T-score of around - 2.33 for men lies above - 2.5. This is likely associated with that older male populations have a higher mean T-score than older female populations. We propose a new category of low BMD status, osteofrailia, for older Caucasian men with T-score ≤ - 2 (T-score ≤ - 2.1 for older Chinese men) who are likely to suffer from hip FFx. The group with T-score ≤ - 2 for older Caucasian men is comparable in prevalence to the group with T-score ≤ - 2.5 for older Caucasian women. However, older men in such category on average have only half the FFx risk as that of older women with osteoporotic T-score.

Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.

OBJECTIVES: Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism. METHODS: SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. RESULTS: SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ. CONCLUSION: SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.

A comparison of radiographic degeneration features of older Chinese women and older Italian Caucasian women with a focus on thoracic spine.

BACKGROUND: Compared with Caucasians, East Asians have a lower incident of back pain, lower prevalence and severity of osteoporotic vertebral fracture and lumbar spine degeneration. AIM: This study compares radiographic spine degeneration features of older Chinese women (as an example of East Asians) and older Italian women (as an example of Caucasians) with a focus on the thoracic spine. METHODS: From two population-based epidemiological studies conducted in Hong Kong, China and Rome, Italy, 297 pairs (mean age: 73.6 years) age-matched older community women's lateral spine radiographs were sampled. Existence (or absence) of seven degeneration features were assessed including: (1) hyper-kyphosis, (2) disc space narrowing (T3/T4 ~ T11/T12), (3) osteoarthritic (OA) wedging (T4 ~ T12), (4) generalised osteophyte formation (T4 ~ T12); (5) acquired short vertebrae (T4 ~ T12), (6) Schmorl node (T4 - L5), (7) disc calcification (T4-L5). RESULTS: Italian women were more likely to have hyper-kyphosis (53.4% vs 25.6%), disc space narrowing (34.4% vs. 17.2%), OA wedging (6.4% vs. 0.67%), Schmorl node (19.5% vs. 4.4%, all P < 0.001). However, there was no statistically significant difference in osteophyte formation (7.7% vs. 9.4%, P > 0.1) and acquired short vertebrae (8.0% vs. 10.4%, P > 0.1). Disc calcification was uncommon among both Chinese and Italians. DISCUSSION AND CONCLUSION: For the first time, this study documented a lower prevalence of a number of thoracic spine degeneration features among Chinese. This study further affirms the concept of a generally healthier spine in older Chinese relative to older Caucasians. The observed differences may reflect a foundational background influence of genetic predisposition that represents an important line of future research.

Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD-HCC through modulating gut microbiota and its metabolites. DESIGN: High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin was administered to HFHC-fed mice. Germ-free mice were transplanted with stools from mice fed different diets to determine the direct role of cholesterol modulated-microbiota in NAFLD-HCC. Gut microbiota was analysed by 16S rRNA sequencing and serum metabolites by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. Faecal microbial compositions were examined in 59 hypercholesterolemia patients and 39 healthy controls. RESULTS: High dietary cholesterol led to the sequential progression of steatosis, steatohepatitis, fibrosis and eventually HCC in mice, concomitant with insulin resistance. Cholesterol-induced NAFLD-HCC formation was associated with gut microbiota dysbiosis. The microbiota composition clustered distinctly along stages of steatosis, steatohepatitis and HCC. Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased sequentially; while Bifidobacterium and Bacteroides were depleted in HFHC-fed mice, which was corroborated in human hypercholesteremia patients. Dietary cholesterol induced gut bacterial metabolites alteration including increased taurocholic acid and decreased 3-indolepropionic acid. Germ-free mice gavaged with stools from mice fed HFHC manifested hepatic lipid accumulation, inflammation and cell proliferation. Moreover, atorvastatin restored cholesterol-induced gut microbiota dysbiosis and completely prevented NAFLD-HCC development. CONCLUSIONS: Dietary cholesterol drives NAFLD-HCC formation by inducing alteration of gut microbiota and metabolites in mice. Cholesterol inhibitory therapy and gut microbiota manipulation may be effective strategies for NAFLD-HCC prevention.

Age and gender dependence of liver diffusion parameters and the possibility that intravoxel incoherent motion modeling of the perfusion component is constrained by the diffusion component.

The aim of this study was to establish reference values for middle-aged subjects and to investigate the age and gender dependence of liver diffusion MRI parameters. The IVIM type of liver diffusion scan was based on a single-shot spin-echo-type echo-planar sequence using a 1.5 T magnet with 16 b-values. Diffusion-derived vessel density (DDVD)(b0b2) or DDVD(b0b10) was the signal difference between b = 0 and b = 2 (or b = 10) s/mm2 images after removing visible vessels. IVIM analysis was performed with full fitting and segmented fitting, and with a threshold b-value of 60 or 200 s/mm2 , and fitting started from b = 2 s/mm2 . Thirty-one men (age range: 25-71 years) and 26 men (age: 22-69 years) had DDVD and IVIM analysis, respectively, while 37 women (age: 20-71 years) and 36 women (age: 20-71 years) had DDVD and IVIM analysis, respectively. DDVD results showed a significant age-related reduction for women. IVIM results for full fitting showed excellent agreement with those for segmented fitting using a threshold b of 60 s/mm2 , but this was less good for results with a threshold b of 200 s/mm2 . As age increased, female subjects' Dslow measure showed a significant reduction, while their PF and Dfast measures showed a significant increase. For the age group of 40-55 years, DDVD(b0b2), DDVD(b0b10), Dslow , PF and Dfast were 12.26 ± 3.90 au/pixel, 16.95 ± 5.45 au/pixel, 1.072 ± 0.067 (10-3 mm2 /s), 0.141 ± 0.025 and 61.0 ± 14.0 (10-3 mm2 /s) for men, and 13.35 ± 3.6 au/pixel, 17.20 ± 3.62 au/pixel, 1.069 ± 0.074 (10-3 mm2 /s), 0.119 ± 0.014 and 57.1 ± 13.2 (10-3 mm2 /s) for women, respectively. DDVD measure of this study suggest that aging is associated with a reduction in liver perfusion. There is a possibility that a lower Dslow measure is associated with artificially higher PF and Dfast measures, and that IVIM modeling of the perfusion component is constrained by the diffusion component.

Macromolecular proton fraction mapping based on spin-lock magnetic resonance imaging.

PURPOSE: In MRI, the macromolecular proton fraction (MPF) is a key parameter of magnetization transfer (MT). It represents the relative amount of immobile protons associated with semi-solid macromolecules involved in MT with free water protons. We aim to quantify MPF based on spin-lock MRI and explore its advantages over the existing MPF-mapping methods. METHODS: In the proposed method, termed MPF quantification based on spin-lock (MPF-SL), off-resonance spin-lock is used to sensitively measure the MT effect. MPF-SL is designed to measure a relaxation rate (Rmpfsl ) that is specific to the MT effect by removing the R1ρ relaxation due to the mobile water and chemical exchange pools. A theory is derived to quantify MPF from the measured Rmpfsl . No prior knowledge of tissue relaxation parameters, including T1 or T2 , is needed to quantify MPF using MPF-SL. The proposed approach is validated with Bloch-McConnell simulations, phantom, and in vivo liver studies at 3.0T. RESULTS: Both Bloch-McConnell simulations and phantom experiments show that MPF-SL is insensitive to variations of the mobile water pool and the chemical exchange pool. MPF-SL is specific to the MT effect and can measure MPF reliably. In vivo liver studies show that MPF-SL can be used to detect collagen deposition in patients with liver fibrosis. CONCLUSION: A novel MPF imaging method based on spin-lock MRI is proposed. The confounding factors are removed, and the measurement is specific to the MT effect. It holds promise for MPF-sensitive diagnostic imaging in clinical settings.

Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

OBJECTIVE: To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APTmean, APT90, APTskewness, and APTkurtosis, respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis. RESULTS: Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APTskewness (HR = 1.98; p = 0.034), DMFS with APTmean (HR = 2.44; p = 0.033), and APT90 (HR = 1.93; p = 0.009), and DFS with APTmean (HR = 2.01; p = 0.016), APT90 (HR = 1.68; p = 0.009), and APTskewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005). CONCLUSION: APTw imaging may potentially predict survival in patients with NPC. KEY POINTS: • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APThigh group is at higher risk of disease relapse than the APTlow group.

Increased chemokine RANTES in synovial fluid and its role in early-stage degenerative temporomandibular joint disease.

BACKGROUND: Degenerative joint disease (DJD) of the temporomandibular joints (TMJs) in adolescents and young adults is closely associated with disc displacement without reduction (DDw/oR). OBJECTIVE: This study aimed to determine the pathogenesis of early-stage TMJ DJD induced by DDw/oR. METHODS: 31 female subjects aged 12-30 years were enrolled, comprising 12 patients with DDw/oR without DJD, 13 with DDw/oR and early-stage DJD, and 6 healthy volunteers. The synovial fluid samples of the subjects were screened for 27 inflammatory-related cytokines using multiple cytokine array. Significantly increased cytokines and a key regulator of osteoclastogenesis "receptor activator of nuclear factor-κB ligand" (RANKL) were further determined by sandwich immunoassay. These factors were also assessed for the possible pathophysiologic actions on RAW264.7 cell proliferation, migration, osteoclastogenesis and bone-resorbing activity using Cell Counting Kit-8, Transwell system, tartrate-resistant acid phosphatase staining and osteo assay plates. RESULTS: Macrophage-derived inflammatory protein-1 beta (MIP-1ß) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to vary significantly in relation to the controls. In contrast to an unchanged concentration of RANKL, a strong increase in the level of RANTES was detected in subjects with DDw/oR and early-stage DJD. MIP-1ß concentrations were only elevated in subjects with DDw/oR without DJD. Functionally, both MIP-1ß and RANTES could enhance macrophage migration in a concentration-dependent manner, while only RANTES exhibited a promoting effect on osteoclast formation and bone-resorbing activity. CONCLUSIONS: Chemokine RANTES was significantly upregulated and might be a key regulator of osteoclastogenesis contributing to DDw/oR-induced early-stage TMJ DJD.

Comparison of tri-exponential decay versus bi-exponential decay and full fitting versus segmented fitting for modeling liver intravoxel incoherent motion diffusion MRI.

OBJECTIVES: To determine whether bi- or tri-exponential models, and full or segmented fittings, better fit the intravoxel incoherent motion (IVIM) imaging signal of healthy livers. METHODS: Diffusion-weighted images were acquired with a 3 T scanner using a respiratory-triggered echo-planar sequence and 16 b-values (0-800 s/mm2 ). Eighteen healthy volunteers had their livers scanned twice in the same session, and then once in another session. Liver parenchyma region-of-interest-based measurements were processed with bi-exponential and tri-exponential models, with both full fitting and segmented fitting (threshold b-value = 200 s/mm2 ). RESULTS: With the signal of all scans averaged, bi-exponential model full fitting showed Dslow  = 1.14 × 10-3  mm2 /s, Dfast  = 193.6 × 10-3  mm2 /s, and perfusion fraction (PF) = 16.9%, and segmented fitting showed Dslow  = 0.98 × 10-3  mm2 /s, Dfast  = 42.2 × 10-3  mm2 /s, and PF = 23.3%. IVIM parameters derived from the tri-exponential model were similar for full fitting and segmented fitting, with slow (D'slow  = 0.98 × 10-3  mm2 /s; F'slow  = 76.4 or 76.6%), fast (D'fast  = 15.1 or 15.4 × 10-3  mm2 /s; F'fast  = 11.8 or 11.7%) and very fast (D'Vfast  = 445.0 or 448.8 × 10-3  mm2 /s; F'Vfast  = 11.8 or 11.7%) diffusion compartments. The tri-exponential model provided an overall better fit than the bi-exponential model. For the bi-exponential model, full fitting provided a better fit at very low and low b-values compared with segmented fitting, with the latter tending to underestimate Dfast ; however, the segmented method demonstrated lower error in signal prediction for high b-values. Compared with full fitting, tri-exponential segmented fitting offered better scan-rescan reproducibility. CONCLUSION: For healthy liver, tri-exponential modeling is preferred to bi-exponential modeling. For the bi-exponential model, segmented fitting underestimates Dfast , but offers a more accurate estimation of Dslow .