Improving the RNA velocity approach with single-cell RNA lifecycle (nascent, mature and degrading RNAs) sequencing technologies.

We presented an experimental method called FLOUR-seq, which combines BD Rhapsody and nanopore sequencing to detect the RNA lifecycle (including nascent, mature, and degrading RNAs) in cells. Additionally, we updated our HIT-scISOseq V2 to discover a more accurate RNA lifecycle using 10x Chromium and Pacbio sequencing. Most importantly, to explore how single-cell full-length RNA sequencing technologies could help improve the RNA velocity approach, we introduced a new algorithm called 'Region Velocity' to more accurately configure cellular RNA velocity. We applied this algorithm to study spermiogenesis and compared the performance of FLOUR-seq with Pacbio-based HIT-scISOseq V2. Our findings demonstrated that 'Region Velocity' is more suitable for analyzing single-cell full-length RNA data than traditional RNA velocity approaches. These novel methods could be useful for researchers looking to discover full-length RNAs in single cells and comprehensively monitor RNA lifecycle in cells.

Predictive markers for head and neck cancer treatment response: T1rho imaging in nasopharyngeal carcinoma.

OBJECTIVES: To investigate the potential of T1rho, a new quantitative imaging sequence for cancer, for pre and early intra-treatment prediction of treatment response in nasopharyngeal carcinoma (NPC) and compare the results with those of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: T1rho and DWI imaging of primary NPCs were performed pre- and early intra-treatment in 41 prospectively recruited patients. The mean preT1rho, preADC, intraT1rho, intraADC, and % changes in T1rho (ΔT1rho%) and ADC (ΔADC%) were compared between residual and non-residual groups based on biopsy in all patients after chemoradiotherapy (CRT) with (n = 29) or without (n = 12) induction chemotherapy (IC), and between responders and non-responders to IC in the subgroup who received IC, using Mann-Whitney U-test. A p-value of < 0.05 indicated statistical significance. RESULTS: Significant early intra-treatment changes in mean T1rho (p = 0.049) and mean ADC (p < 0.01) were detected (using paired t-test), most showing a decrease in T1rho (63.4%) and an increase in ADC (95.1%). Responders to IC (n = 17), compared to non-responders (n = 12), showed higher preT1rho (64.0 ms vs 66.5 ms) and a greater decrease in ΔT1rho% (- 7.5% vs 1.3%) (p < 0.05). The non-residual group after CRT (n = 35), compared to the residual group (n = 6), showed higher intraADC (0.96 vs 1.09 × 10-3 mm2/s) and greater increase in ΔADC% (11.7% vs 27.0%) (p = 0.02). CONCLUSION: Early intra-treatment changes are detectable on T1rho and show potential to predict tumour shrinkage after IC. T1rho may be complementary to DWI, which, unlike T1rho, did not predict response to IC but did predict non-residual disease after CRT. CLINICAL RELEVANCE STATEMENT: T1rho has the potential to complement DWI in the prediction of treatment response. Unlike DWI, it predicted shrinkage of the primary NPC after IC but not residual disease after CRT. KEY POINTS: Changes in T1rho were detected early during cancer treatment for NPC. Pre-treatment and early intra-treatment change in T1rho predicted response to IC, but not residual disease after CRT. T1rho can be used to complement DWI with DWI predicting residual disease after CRT.

Detecting Early-Stage Liver Fibrosis Using Macromolecular Proton Fraction Mapping Based on Spin-Lock MRI: Preliminary Observations.

BACKGROUND: Liver fibrosis is characterized by macromolecule depositions. Recently, a novel technology termed macromolecular proton fraction quantification based on spin-lock magnetic resonance imaging (MPF-SL) is reported to measure macromolecule levels. HYPOTHESIS: MPF-SL can detect early-stage liver fibrosis by measuring macromolecule levels in the liver. STUDY TYPE: Retrospective. SUBJECTS: Fifty-five participants, including 22 with no fibrosis (F0) and 33 with early-stage fibrosis (F1-2), were recruited. FIELD STRENGTH/SEQUENCE: 3 T; two-dimensional (2D) MPF-SL turbo spin-echo sequence, 2D spin-lock T1rho turbo spin-echo sequence, and multi-slice 2D gradient echo sequence. ASSESSMENT: Macromolecular proton fraction (MPF), T1rho, liver iron concentration (LIC), and fat fraction (FF) biomarkers were quantified within regions of interest. STATISTICAL TESTS: Group comparison of the biomarkers using Mann-Whitney U tests; correlation between the biomarkers assessed using Spearman's rank correlation coefficient and linear regression with goodness-of-fit; fibrosis stage differentiation using receiver operating characteristic curve (ROC) analysis. P-value < 0.05 was considered statistically significant. RESULTS: Average T1rho was 41.76 ± 2.94 msec for F0 and 41.15 ± 3.73 msec for F1-2 (P = 0.60). T1rho showed nonsignificant correlation with either liver fibrosis (ρ = -0.07; P = 0.61) or FF (ρ = -0.14; P = 0.35) but indicated a negative correlation with LIC (ρ = -0.66). MPF was 4.73 ± 0.45% and 5.65 ± 0.81% for F0 and F1-2 participants, respectively. MPF showed a positive correlation with liver fibrosis (ρ = 0.59), and no significant correlations with LIC (ρ = 0.02; P = 0.89) or FF (ρ = 0.05; P = 0.72). The area under the ROC curve was 0.85 (95% confidence interval [CI] 0.75-0.95) and 0.55 (95% CI 0.39-0.71; P = 0.55) for MPF and T1rho to discriminate between F0 and F1-2 fibrosis, respectively. DATA CONCLUSION: MPF-SL has the potential to diagnose early-stage liver fibrosis and does not appear to be confounded by either LIC or FF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Dual-Ligand Near-Infrared Luminescent Lanthanide-Based Metal-Organic Framework Coupled with In Vivo Microdialysis for Highly Sensitive Ratiometric Detection of Zn2+ in a Mouse Model of Alzheimer's Disease.

Zinc, which is the second most abundant trace element in the human central nervous system, is closely associated with Alzheimer's disease (AD). However, attempts to develop highly sensitive and selective sensing systems for Zn2+ in the brain have not been successful. Here, we used a one-step solvothermal method to design and prepare a metal-organic framework (MOF) containing the dual ligands, terephthalic acid (H2BDC) and 2,2':6',2″-terpyridine (TPY), with Eu3+ as a metal node. This MOF is denoted as Eu-MOF/BDC-TPY. Adjustment of the size and morphology of Eu-MOF/BDC-TPY allowed the dual ligands to produce multiple luminescence peaks, which could be interpreted via ratiometric fluorescence to detect Zn2+ using the ratio of Eu3+-based emission, as the internal reference, and ligand-based emission, as the indicator. Thus, Eu-MOF/BDC-TPY not only displayed higher selectivity than other metal cations but also offered a highly accurate, sensitive, wide linear, color change-based technique for detecting Zn2+ at concentrations ranging from 1 nM to 2 µM, with a low limit of detection (0.08 nM). Moreover, Eu-MOF/BDC-TPY maintained structural stability and displayed a fluorescence intensity of at least 95.4% following storage in water for 6 months. More importantly, Eu-MOF/BDC-TPY sensed the presence of Zn2+ markedly rapidly (within 5 s), which was very useful in practical application. Furthermore, the results of our ratiometric luminescent method-based analysis of Zn2+ in AD mouse brains were consistent with those obtained using inductively coupled plasma mass spectrometry.

Characterization and correction of the effects of hepatic iron on T1ρ relaxation in the liver at 3.0T.

PURPOSE: Quantitative T1ρ imaging is an emerging technique to assess the biochemical properties of tissues. In this paper, we report our observation that liver iron content (LIC) affects T1ρ quantification of the liver at 3.0T field strength and develop a method to correct the effect of LIC. THEORY AND METHODS: On-resonance R1ρ (1/T1ρ ) is mainly affected by the intrinsic R2 (1/T2 ), which is influenced by LIC. As on-resonance R1ρ is closely related to the Carr-Purcell-Meiboom-Gill (CPMG) R2 , and because the calibration between CPMG R2 and LIC has been reported at 1.5T, a correction method was proposed to correct the R2 contribution to the R1ρ . The correction coefficient was obtained from the calibration results and related transformed factors. To compensate for the difference between CPMG R2 and R1ρ , a scaling factor was determined using the values of CPMG R2 and R1ρ , obtained simultaneously from a single breath-hold from volunteers. The livers of 110 subjects were scanned to validate the correction method. RESULTS: LIC was significantly correlated with R1ρ in the liver. However, when the proposed correction method was applied to R1ρ , LIC and the iron-corrected R1ρ were not significantly correlated. CONCLUSION: LIC can affect T1ρ in the liver. We developed an iron-correction method for the quantification of T1ρ in the liver at 3.0T.

MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesis.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary GN worldwide. Circulating immune complexes form that are prone to deposition in the mesangium, where they trigger glomerular inflammation. A growing body of evidence suggests that dysregulated expression of microRNAs in IgAN may play a significant role in establishing the disease phenotype. METHODS: We generated single miR-23b-3p(miR-23b) knockout mice using CRISPR-Cas9. RESULTS: In humans, miR-23b levels are downregulated in kidney biopsies and sera of patients with IgAN, and serum miR-23b levels are negatively correlated with serum IgA1 levels. We show that miR-23b-/- mice develop an IgAN-like phenotype of mesangial IgA and C3 deposition associated with development of albuminuria, hypertension, an elevated serum creatinine, and dysregulated mucosal IgA synthesis. Dysregulation of IgA production is likely mediated by the loss of miR-23b-mediated suppression of activation-induced cytidine deaminase in mucosal B cells. In addition, we show that loss of miR-23b increases the susceptibility of the kidney to progressive fibrosis through loss of regulation of expression of gremlin 2 and IgA accumulation through downregulation of the transferrin receptor. CONCLUSIONS: Our findings suggest an indispensable role for miR-23b in kidney disease, and in particular, IgAN. miR-23b may in the future offer a novel therapeutic target for the treatment of IgAN.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Chemical-shift encoding-based water-fat separation with multifrequency fat spectrum modeling in spin-lock MRI.

PURPOSE: Chemical exchange saturation transfer is used commonly to generate MRI contrast based on the chemical exchange effect. The spin-lock techniques can also be used to probe the chemical exchange and other molecular motion processes in tissues. The presence of fat can cause errors in spin-lock MRI. Signals from fat are typically suppressed based on spectral selectivity or T1 nulling approaches in spin-lock imaging. However, these methods cannot be used to suppress fat signals from multiple fat peaks. To address this problem, we report chemical-shift encoding-based water-fat separation approaches with multifrequency fat spectrum modeling. METHODS: Both the conventional spin-lock and the adiabatic continuous-wave constant-amplitude spin lock (ACCSL) with multi-echo acquisitions are investigated for chemical-shift encoding-based water-fat separation in spin-lock imaging. A comparison is made of reconstructions based on 3 models: a single-peak fat spectrum model, a standard precalibrated proton density 6-peak fat spectrum model, and the self-calibrated relaxation-dependent 3-peak fat spectrum model. Comparisons were performed using Bloch simulations, phantom, and in vivo experiments at 3 T. RESULTS: Conventional spin-lock acquisitions cannot be used for reliable water-fat separation with a multipeak fat spectrum model. Water-fat separation based on ACCSL acquisitions achieves superior performance compared with the use of conventional spin-lock acquisitions. The best result is achieved from ACCSL acquisition with self-calibrated relaxation-dependent multipeak fat spectrum modeling. CONCLUSION: The ACCSL acquisition can be used for chemical-shift encoding-based water-fat separation with multipeak fat spectrum modeling. This approach has the potential to improve quantitative analysis using spin-lock MRI for assessing the biochemical properties of tissues.

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.

[Coridius Decoction increases penile erection hardness, IIEF-5 scores and testosterone level in patients with erectile dysfunction].

OBJECTIVE: To explore the effect of Coridius Decoction on penile erection hardness, IIEF-5 scores and the testosterone level in ED patients. METHODS: We selected 120 ED patients diagnosed and treated in our hospital between July 2018 and January 2020 and, using the random number table, divided them into a control (n = 55) and an observation (n = 65), the former treated with oral sildenafil and the latter with warm Coridius Decoction in addition, both for 8 weeks and followed up for 6 months. We compared the TCM syndrome scores, clinical effects, penile erection hardness, IIEF-5 scores, testosterone (T) level and adverse reactions between the two groups of patients. RESULTS: The TCM syndrome score, compared with the baseline, was significantly decreased in the observation (9.81 ± 0.61 vs 17.63 ± 1.16, P < 0.05) and the control group (17.56 ± 1.23 vs 13.18 ± 0.75, P < 0.05) after treatment, even lower in the former than in the latter group (P < 0.01). The total therapeutic effectiveness rate was markedly higher in the observation group than in the control (92.31% ï¼»60/65ï¼½ vs 80.00% ï¼»44/55ï¼½, P < 0.05). After medication, the erection hardness score (EHS) was dramatically higher than the baseline in the observation (4.21 ± 0.55 vs 2.55 ± 0.73, P < 0.01) and the control group (3.14 ± 0.54 vs 2.61 ± 0.73, P < 0.01), and so were the IIEF-5 score (18.58 ± 5.26 vs 12.00 ± 4.68, P < 0.05 and 15.29 ± 4.70 vs 11.94 ± 5.54, P < 0.05) and the T level (ï¼»13.27 ± 4.21ï¼½ vs ï¼»9.43 ± 4.31ï¼½ nmol/L, P < 0.05 and ï¼»10.74 ± 4.15ï¼½ vs ï¼»9.01 ± 4.72ï¼½ nmol/L, P < 0.05), both even higher in the former than in the latter group (P < 0.01). There were no statistically significant differences in the incidence rates of adverse reactions between the observation and control groups (6.15% ï¼»4/65ï¼½ vs 3.64% ï¼»2/55ï¼½, P = 0.834). CONCLUSIONS: Coridius Decoction is safe and effective for the treatment of ED, which can significantly improve the clinical symptoms, increase penile erectile hardness and the T level, and repair the erectile function of the patient.

Probing chemical exchange using quantitative spin-lock R1ρ asymmetry imaging with adiabatic RF pulses.

PURPOSE: CEST is commonly used to probe the effects of chemical exchange. Although R1ρ asymmetry quantification has also been described as a promising option for detecting the effects of chemical exchanges, the existing acquisition approaches are highly susceptible to B1 RF and B0 field inhomogeneities. To address this problem, we report a new R1ρ asymmetry imaging approach, AC-iTIP, which is based on the previously reported techniques of irradiation with toggling inversion preparation (iTIP) and adiabatic continuous wave constant amplitude spin-lock RF pulses (ACCSL). We also derived the optimal spin-lock RF pulse B1 amplitude that yielded the greatest R1ρ asymmetry. METHODS: Bloch-McConnell simulations were used to verify the analytical formula derived for the optimal spin-lock RF pulse B1 amplitude. The performance of the AC-iTIP approach was compared to that of the iTIP approach based on hard RF pulses and the R1ρ -spectrum acquired using adiabatic RF pulses with the conventional fitting method. Comparisons were performed using Bloch-McConnell simulations, phantom, and in vivo experiments at 3.0T. RESULTS: The analytical prediction of the optimal B1 was validated. Compared to the other 2 approaches, the AC-iTIP approach was more robust under the influences of B1 RF and B0 field inhomogeneities. A linear relationship was observed between the measured R1ρ asymmetry and the metabolite concentration. CONCLUSION: The AC-iTIP approach could probe the chemical exchange effect more robustly than the existing R1ρ asymmetry acquisition approaches. Therefore, AC-iTIP is a promising technique for metabolite imaging based on the chemical exchange effect.

Distinguishing early-stage nasopharyngeal carcinoma from benign hyperplasia using intravoxel incoherent motion diffusion-weighted MRI.

OBJECTIVES: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities. METHODS: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant. RESULTS: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10-3 mm2/s), ADC0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10-3 mm2/s), ADC300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10-3 mm2/s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10-3 mm2/s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10-3 mm2/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia. CONCLUSION: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC300-1000 mean were the most promising parameters. KEY POINTS: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.

Dependence of intravoxel incoherent motion diffusion MR threshold b-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance.

BACKGROUND: Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value. PURPOSE: To explore how threshold b-value impacts PF ( f), Dslow ( D), and Dfast ( D*) values and their performance for liver fibrosis detection. MATERIAL AND METHODS: Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm2. Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm2 were compared. PF, Dslow, and Dfast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients. RESULTS: Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher Dslow and Dfast measurements. The dependence of PF, Dslow, and Dfast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), Dslow (Dslow < 1.239 × 10-3 mm2/s), and Dfast (Dfast < 20.85 × 10-3 mm2/s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1. CONCLUSION: For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm2 improves IVIM differentiation between healthy livers and fibrotic livers.

Amide proton transfer MRI detects early changes in nasopharyngeal carcinoma: providing a potential imaging marker for treatment response.

PURPOSE: To determine if treatment of nasopharyngeal carcinoma (NPC) induces early changes in amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI), and to perform a preliminary evaluation of APTw imaging in response assessment. METHODS: Sixteen patients with NPC planned for treatment with radiotherapy and/or chemotherapy underwent APTw imaging of the primary tumour pre-treatment and 2-week intra-treatment. Difference in pre- and intra-treatment APT mean (APTmean) was compared using the Wilcoxon signed rank test. Differences in APTmean and percentage change (%Δ) in APTmean were compared between responders and non-responders based on the outcome at 6 months, using the Mann-Whitney U test. RESULTS: APTmean decreased in 9/16 (56.3%) and increased in 7/16 (43.7%) with no significant difference between the pre- and intra-treatment APT values for the whole group (p > 0.05). NPC showed response in 11/16 (68.8%) and non-response in 5/11 (31.2%). There were significant differences between the %Δ of responders and non-responders for APTmean (p = 0.01). Responders showed %Δ decrease in APTmean of - 23.12% while non-responders showed a %Δ increase in APTmean of + 102.28%. CONCLUSION: APT value changes can be detected in early intra-treatment. Intra-treatment %Δ APTmean shows potential in predicting short-term outcome.

Head and Neck Tumors: Amide Proton Transfer MRI.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in the characterization of head and neck tumors. Materials and Methods This retrospective study of APT imaging included 117 patients with 70 nasopharyngeal undifferentiated carcinomas (NUCs), 26 squamous cell carcinomas (SCCs), eight non-Hodgkin lymphomas (NHLs), and 13 benign salivary gland tumors (BSGTs). Normal tissues were examined in 25 patients. The APT means of malignant tumors, normal tissues, and benign tumors were calculated and compared with the Student t test and analysis of variance. The added value of the mean APT to the mean apparent diffusion coefficient (ADC) for differentiating malignant and benign tumors was evaluated by using receiver operating characteristic analysis and integrated discrimination index. Results The mean APT of malignant tumors (2.40% ± 0.97 [standard deviation]) was significantly higher than that of brain tissue (1.13% ± 0.43), muscle tissue (0.23% ± 0.73), and benign tumors (1.32% ± 1.20) (P < .001). There were no differences between malignant groups (NUC, 2.37% ± 0.90; SCC, 2.41% ± 1.16; NHL, 2.65% ± 0.89; P = .45 to P = .86). The mean ADC of malignant tumors ([0.85 ± 0.17] × 10-3 mm2/sec) was significantly lower than that of benign tumors ([1.46 ± 0.47] × 10-3 mm2/sec) (P = .001). Adding APT to ADC increased the area under the curve from 0.87 to 0.96, with an integrated discrimination index of 7.6% (P = .13). Conclusion These preliminary data demonstrate differences in amide proton transfer (APT) mean of malignant tumors, normal tissues, and benign tumors, although APT mean could not be used to differentiate between malignant tumor groups. APT imaging has the potential to be of added value to apparent diffusion coefficient in differentiating malignant from benign tumors.

On-resonance and off-resonance continuous wave constant amplitude spin-lock and T1ρ quantification in the presence of B1 and B0 inhomogeneities.

Spin-lock MRI is a valuable diagnostic imaging technology, as it can be used to probe the macromolecule environment of tissues. Quantitative T1ρ imaging is one application of spin-lock MRI that is reported to be promising for a number of clinical applications. Spin-lock is often performed with a continuous RF wave at a constant RF amplitude either on resonance or off resonance. However, both on- and off-resonance spin-lock approaches are susceptible to B1 and B0 inhomogeneities, which results in image artifacts and quantification errors. In this work, we report a continuous wave constant amplitude spin-lock approach that can achieve negligible image artifacts in the presence of B1 and B0 inhomogeneities for both on- and off-resonance spin-lock. Under the adiabatic condition, by setting the maximum B1 amplitude of the adiabatic pulses equal to the B1 amplitude of spin-lock RF pulse, the spins are ensured to align along the effective field throughout the spin-lock process. We show that this results in simultaneous compensation of B1 and B0 inhomogeneities for both on- and off-resonance spin-lock. The relaxation effect during the entire adiabatic half passage (AHP) and reverse AHP, and the stationary solution of the Bloch-McConnell equation present at off-resonance frequency offset, are considered in the revised relaxation model. We demonstrate that these factors create a direct current component to the conventional relaxation model. In contrast to the previously reported dual-acquisition method, the revised relaxation model just requires one acquisition to perform quantification. The simulation, phantom, and in vivo experiments demonstrate that the proposed approach achieves superior image quality compared with the existing methods, and the revised relaxation model can perform T1ρ quantification with one acquisition instead of two.

Breath-hold black-blood T1rho mapping improves liver T1rho quantification in healthy volunteers.

Background Recent researches suggest that T1rho may be a non-invasive and quantitative technique for detecting and grading liver fibrosis. Purpose To compare a multi-breath-hold bright-blood fast gradient echo (GRE) imaging and a single breath-hold single-shot fast spin echo (FSE) imaging with black-blood effect for liver parenchyma T1rho measurement and to study liver physiological T1rho value in healthy volunteers. Material and Methods The institutional Ethics Committee approved this study. 28 healthy participants (18 men, 10 women; age = 29.6 ± 5.1 years) underwent GRE liver T1rho imaging, and 20 healthy participants (10 men, 10 women; age = 36.9 ± 10.3 years) underwent novel black-blood FSE liver T1rho imaging, both at 3T with spin-lock frequency of 500 Hz. The FSE technique allows simultaneous acquisition of four spin lock times (TSLs; 1 ms, 10 ms, 30 ms, 50msec) in 10 s. Results For FSE technique the intra-scan repeatability intraclass correlation coefficient (ICC) was 0.98; while the inter-scan reproducibility ICC was 0.82 which is better than GRE technique's 0.76. Liver T1rho value in women tended to have a higher value than T1rho values in men (FSE: 42.28 ± 4.06 ms for women and 39.13 ± 2.12 ms for men; GRE: 44.44 ± 1.62 ms for women and 42.36 ± 2.00 ms for men) and FSE technique showed liver T1rho value decreased slightly as age increased. Conclusion Single breath-hold black-blood FSE sequence has better scan-rescan reproducibility than multi-breath-hold bright-blood GRE sequence. Gender and age dependence of liver T1rho in healthy participants is observed, with young women tending to have a higher T1rho measurement.