Motion robust coronary MR angiography using zigzag centric ky-kz trajectory and high-resolution deep learning reconstruction.

PURPOSE: To develop a new MR coronary angiography (MRCA) technique by employing a zigzag fan-shaped centric ky-kz k-space trajectory combined with high-resolution deep learning reconstruction (HR-DLR). METHODS: All imaging data were acquired from 12 healthy subjects and 2 patients using two clinical 3-T MR imagers, with institutional review board approval. Ten healthy subjects underwent both standard 3D fast gradient echo (sFGE) and centric ky-kz k-space trajectory FGE (cFGE) acquisitions to compare the scan time and image quality. Quantitative measures were also performed for signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as sharpness of the vessel. Furthermore, the feasibility of the proposed cFGE sequence was assessed in two patients. For assessing the feasibility of the centric ky-kz trajectory, the navigator-echo window of a 30-mm threshold was applied in cFGE, whereas sFGE was applied using a standard 5-mm threshold. Image quality of MRCA using cFGE with HR-DLR and sFGE without HR-DLR was scored in a 5-point scale (non-diagnostic = 1, fair = 2, moderate = 3, good = 4, and excellent = 5). Image evaluation of cFGE, applying HR-DLR, was compared with sFGE without HR-DLR. Friedman test, Wilcoxon signed-rank test, or paired t tests were performed for the comparison of related variables. RESULTS: The actual MRCA scan time of cFGE with a 30-mm threshold was acquired in less than 5 min, achieving nearly 100% efficiency, showcasing its expeditious and robustness. In contrast, sFGE was acquired with a 5-mm threshold and had an average scan time of approximately 15 min. Overall image quality for MRCA was scored 3.3 for sFGE and 2.7 for cFGE without HR-DLR but increased to 3.6 for cFGE with HR-DLR and (p < 0.05). The clinical result of patients obtained within 5 min showed good quality images in both patients, even with a stent, without artifacts. Quantitative measures of SNR, CNR, and sharpness of vessel presented higher in cFGE with HR-DLR. CONCLUSION: Our findings demonstrate a robust, time-efficient solution for high-quality MRCA, enhancing patient comfort and increasing clinical throughput.

Plasma prolactin axis shift from placental to pituitary origin in late prepartum mice.

The placenta secretes a prolactin (PRL)-like hormone PRL3B1 (placental lactogen II), a luteotropic hormone essential for maintaining pregnancy until labor in mice. A report from 1984 examined the secretion pattern of PRL3B1 in prepartum mice. In the current study, we found contradictory findings in the secretion pattern that invalidate the previous report. By measuring maternal plasma PRL3B1 and PRL every 4 hrs from gestational day 17 (G17), we newly discovered that maternal plasma PRL3B1 levels decrease rapidly in prepartum C57BL/6 mice. Interestingly, the onset of this decline coincided with the PRL surge at G18, demonstrating a plasma prolactin axis shift from placental to pituitary origin. We also found that maternal plasma progesterone regression precedes the onset of the PRL shift. The level of Prl3b1 mRNA was determined by RT-qPCR in the placenta and remained stable until parturition, implying that PRL3B1 peptide production or secretion was suppressed. We hypothesized that production of the PRL family, the 25 paralogous PRL proteins exclusively expressed in mice placenta, would decrease alongside PRL3B1 during this period. To investigate this hypothesis and to seek proteomic changes, we performed a shotgun proteome analysis of the placental tissue using data-independent acquisition mass spectrometry (DIA-MS). Up to 5,891 proteins were identified, including 17 PRL family members. Relative quantitative analysis between embryonic day 17 (E17) and E18 placentas showed no significant difference in the expression of PRL3B1 and most PRL family members except PRL7C1. These results suggest that PRL3B1 secretion from the placenta is suppressed at G18 (E18).

Multiparametric exchange protons using Z-spectrum analysis proton (ZAP) and CEST on phantoms and human abdomen.

PURPOSE: This study aims to investigate a multiparametric exchange proton approach using CEST and Z-spectrum analysis protons (ZAP) in human abdominal organs, focusing on tissue differentiation for a potential early biomarker of abnormality. Prior to human studies, CEST and ZAP effects were studied in phantoms containing exchange protons. METHODS: Phantoms composed of iopamidol and iohexol solutions with varying pH levels, along with 12 human subjects, were scanned on a clinical 3T MR scanner. Subsequent ZAP analyses employed a two-Lorentzian pool model to provide free and restricted apparent T 2 f , r ex $$ {\mathrm{T}}_{2\ \mathrm{f},\mathrm{r}}^{\mathrm{ex}} $$ , and their fractions for data acquired across a wide range of offset frequencies (±100 kHz or ± 800 ppm), while a narrower range (±7 ppm or ± 900 Hz) was used for CEST analysis to estimate magnetization transfer ratio asymmetry (MTRAsym) for exchange protons like hydroxyl (OH), amine (NH2), and amide (NH), resonating ˜1, 2, and 3.5 ppm, respectively. Differences in ZAP metrics across various organs were statistically analyzed using one-way analysis of variance (ANOVA). RESULTS: The phantom study differentiated contrast agents based on resonance peaks detected from CEST analysis, while ZAP metrics showed sensitivity to pH variations. In human, ZAP metrics revealed significant differences in abdominal organs, with a subgroup study indicating changes in ZAP metrics due to the presence of gallstones. CONCLUSION: CEST and ZAP techniques demonstrated promise in specific CEST protons and wide range ZAP protons and identifying tissue-specific characteristics. The preliminary findings underscore the necessity for more extensive study involving a broader subject pool to potentially establish biomarkers for diseased states.

Non-contrast MRI of micro-vascularity of the feet and toes.

PURPOSE: This study aimed to develop novel non-contrast MR perfusion techniques for assessing micro-vascularity of the foot in human subjects. METHODS: All experiments were performed on a clinical 3 T scanner using arterial spin labeling (ASL). Seven healthy subjects (30-72 years old, 5 males and 2 females) were enrolled and bilateral feet were imaged with tag-on and tag-off alternating inversion recovery spin labeling for determining micro-vascularity. We compared an ASL technique with 1-tag against 4-tag pulses. For perfusion, we determined signal increase ratio (SIR) at varying inversion times (TI) from 0.5 to 2 s. SIR versus TI data were fit to determine perfusion metrics of peak height (PH), time to peak (TTP), full width at half maximum (FWHM), area under the curve (AUC), and apparent blood flow (aBF) in the distal foot and individual toes. Using analysis of variance (ANOVA), effects of tag pulse and region of interest (ROI) on the mean perfusion metrics were assessed. In addition, a 4-tag pulse perfusion experiment was performed on patients with peripheral artery disease (PAD) and Raynaud's disease. RESULTS: Using our MR perfusion techniques, SIR versus TI data showed well-defined leading and trailing edges, with a peak near TI of 0.75-1.0 s and subsiding quickly to near zero by TI of 2 s, particularly when 4-tag pulses were used. When imaged with 4-tag pulse, we found significantly greater values in perfusion metrics, as compared to 1-tag pulse. The patients with PAD and Raynaud's disease showed a reduced or scattered perfusion curves compared to the healthy control. CONCLUSION: MR perfusion imaging of the distal foot shows greater SIR and perfusion metrics with the 4-tag pulse compared to the 1-tag pulse technique. This will likely benefit those with low perfusion due to aging, PAD, diabetic foot, and other vascular diseases.

Aliphatic and Olefinic Fat Suppression in the Orbit Using Polarity-altered Spectral and Spatial Selective Acquisition (PASTA) with Opposed Phase.

PURPOSE: Fatty acid composition of the orbit makes it challenging to achieve complete fat suppression during orbit MR imaging. Implementation of a fat suppression technique capable of suppressing signals from saturated (aliphatic) and unsaturated (olefinic or protons at double-bonded carbon sites) fat would improve the visualization of an optical nerve. Furthermore, the ability to semi-quantify the fractions of aliphatic and olefinic fat may potentially provide valuable information in assessing orbit pathology. METHODS: A phantom study was conducted on various oil samples on a clinical 3 Tesla scanner. The imaging protocol included three 2D fast spin echo (FSE) sequences: in-phase, polarity-altered spectral and spatial selective acquisition (PASTA), and a combination of PASTA with opposed phase in olefinic and aliphatic chemical shift. The results were validated against high-resolution 11.7T NMR and compared with images acquired with spectral attenuated inversion recovery (SPAIR) and chemical shift selective (CHESS) fat suppression techniques. In-vivo data were acquired on eight healthy subjects and were compared with the prior histological studies. RESULTS: PASTA with opposed phase achieved complete suppression of fat signals in the orbits and provided images of well-delineated optical nerves and muscles in all subjects. The olefinic fat fraction in the olive, walnut, and fish oil phantoms at 3T was found to be 5.0%, 11.2%, and 12.8%, respectively, whereas 11.7T NMR provides the following olefinic fat fractions: 6.0% for olive, 11.5% for walnut, and 12.6% for fish oils. For the in-vivo study, on average, olefinic fat accounted for 9.9% ± 3.8% of total fat while the aliphatic fat fraction was 90.1% ± 3.8%, in the normal orbits. CONCLUSION: We have introduced a new fat suppression technique using PASTA with opposed phase and applied it to human orbits. The purposed method achieves an excellent orbital fat suppression and the quantification of aliphatic and olefinic fat signals.

Physical Exercise Alters Egress Pathways for Intrinsic CSF Outflow: An Investigation Performed with Spin-labeling MR Imaging.

PURPOSE: Cerebrospinal fluid (CSF) clearance is essential for maintaining a healthy brain and cognition by removal of metabolic waste from the central nervous system. Physical exercise has been shown to improve human health; however, the effect of physical exercise on intrinsic CSF outflow in humans remains unexplored. The purpose of this study was to investigate intrinsic CSF outflow pathways and quantitative metrics of healthy individuals with active and sedentary lifestyles. In addition, the effect of exercise was investigated among the sedentary subjects before and after 3 weeks of physical activity. METHODS: This study was performed on 18 healthy adults with informed consent, using a clinical 3-Tesla MRI scanner. We classified participants into two groups based on reported time spent sitting per day (active group: < 7 hours sitting per day and sedentary group: ≥ 7 hours sitting per day). To elucidate the effect of exercise, sedentary individuals increased their activity to 3.5 hours for 3 weeks. RESULTS: We show that there are two intrinsic CSF egress pathways of the dura mater and lower parasagittal dura (PSD). The adults with an active lifestyle had greater intrinsic CSF outflow metrics than adults with a more sedentary lifestyle. However, after increased physical activity, the sedentary group showed improved CSF outflow metrics. This improvement was particularly notable at the lower PSD, where outflow metrics were highest among the active group. CONCLUSION: Our findings describe the relationship between physical activity and intrinsic CSF outflow and show a potential selective outflow pathway with increasing physical activity in the lower PSD pathway, potentially from the perivascular space or cortical venous subpial space.

Lung T2 * mapping using 3D ultrashort TE with tight intervals δTE.

PURPOSE: To develop 3D ultrashort-TE (UTE) sequences with tight TE intervals (δTE), allowing for accurate T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping of lungs under free breathing. METHODS: We have implemented a four-echo UTE sequence with δTE (< 0.5 ms). A Monte-Carlo simulation was performed to identify an optimal number of echoes that would result in a significant improvement in the accuracy of the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ fit within an acceptable scan time. A validation study was conducted on a phantom with known short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ values (< 5 ms). The scanning protocol included a combination of a standard multi-echo UTE with six echoes (2.2-ms intervals) and a new four-echo UTE (TE < 2 ms) with tight TE intervals δTE. The human imaging was performed at 3 T on 6 adult volunteers. T 2 * $$ {\mathrm{T}}_2^{\ast } $$ mapping was performed with mono-exponential and bi-exponential models. RESULTS: The simulation for the proposed 10-echo acquisition predicted over 2-fold improvement in the accuracy of estimating the short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ compared with the regular six-echo acquisition. In the phantom study, the T 2 * $$ {\mathrm{T}}_2^{\ast } $$ was measured up to three times more accurately compared with standard six-echo UTE. In human lungs, T 2 * $$ {\mathrm{T}}_2^{\ast } $$ maps were successfully obtained from 10 echoes, yielding average values T 2 * $$ {\mathrm{T}}_2^{\ast } $$ = 1.62 ± 0.48 ms for mono-exponential and T 2 s * $$ {\mathrm{T}}_{2s}^{\ast } $$ = 1.00 ± 0.53 ms for bi-exponential models. CONCLUSION: A UTE sequence using δTE was implemented and validated on short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ phantoms. The sequence was successfully applied for lung imaging; the bi-exponential signal model fit for human lung imaging may provide valuable insights into the diseased human lungs.

3D T1rho sequences with FASE, UTE, and MAPSS acquisitions for knee evaluation.

PURPOSE: For biochemical evaluation of soft tissues of the knee, T1rho magnetic resonance imaging (MRI) has been proposed. Purpose of this study was to compare three T1rho sequences based on fast advanced spin echo (FASE), ultrashort echo time (UTE), and magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) acquisitions for the knee evaluation. MATERIALS AND METHODS: We developed two T1rho sequences using 3D FASE or 3D radial UTE acquisitions. 3D MAPSS T1rho was provided by the manufacturer. Agarose phantoms with varying concentrations were imaged. Additionally, bilateral knees of asymptomatic subjects were imaged sagittally. T1rho values of the phantoms and 4 regions of interest (ROI) of the knees (i.e., anterior and posterior meniscus, femoral and tibial cartilage) were determined. RESULTS: In phantoms, all T1rho values monotonically decreased with increasing agarose concentration. 3D MAPSS T1rho values of 51, 34, and 38 ms were found for 2, 3, and 4% agarose, respectively, similar to published values on another platform. In the knee, the raw images were detailed with good contrast. Cartilage and meniscus T1rho values varied with the pulse sequence, being the lowest in the 3D UTE T1rho sequence. Comparing different ROIs, menisci generally had lower T1rho values compared to cartilage, as expected in healthy knees. CONCLUSION: We have successfully developed and implemented the new T1rho sequences and validated them using agarose phantoms and volunteer knees. All sequences were optimized to be clinically feasible (~ 5 min or less) and yielded satisfactory image quality and T1rho values consistent with the literature.

Age-related Decline of Intrinsic Cerebrospinal Fluid Outflow in Healthy Humans Detected with Non-contrast Spin-labeling MR Imaging.

PURPOSE: Clearance of cerebrospinal fluid (CSF) is important for the removal of toxins from the brain, with implications for neurodegenerative diseases. Imaging evaluation of CSF outflow in humans has been limited, relying on venous or invasive intrathecal injections of contrast agents. The objective of this study was to introduce a novel spin-labeling MRI technique to detect and quantify the movement of endogenously tagged CSF, and then apply it to evaluate CSF outflow in normal humans of varying ages. METHODS: This study was performed on a clinical 3-Tesla MRI scanner in 16 healthy subjects with an age range of 19-71 years with informed consent. Our spin-labeling MRI technique applies a tag pulse on the brain hemisphere, and images the outflow of the tagged CSF into the superior sagittal sinus (SSS). We obtained 3D images in real time, which was analyzed to determine tagged-signal changes in different regions of the meninges involved in CSF outflow. Additionally, the signal changes over time were fit to a signal curve to determine quantitative flow metrics. These were correlated against subject age to determine aging effects. RESULTS: We observed the signal of the tagged CSF moving from the dura mater and parasagittal dura, and finally draining into the SSS. In addition, we observed a possibility of another pathway which is seen in some young subjects. Furthermore, quantitative CSF outflow metrics were shown to decrease significantly with age. CONCLUSION: We demonstrate a novel non-invasive MRI technique identifying two intrinsic CSF clearance pathways, and observe an age-related decline of CSF flow metrics in healthy subjects. Our work provides a new opportunity to better understand the relationships of these CSF clearance pathways during the aging process, which may ultimately provide insight into the age-related prevalence of neurodegenerative diseases.

Time-Resolved Noncontrast Magnetic Resonance Perfusion Imaging of Paraspinal Muscles.

BACKGROUND: While evaluation of blood perfusion in lumbar paraspinal muscles is of interest in low back pain, it has not been performed using noncontrast magnetic resonance (MR) techniques. PURPOSE: To introduce a novel application of a time-resolved, noncontrast MR perfusion technique for paraspinal muscles and demonstrate effect of exercise on perfusion parameters. STUDY TYPE: Longitudinal. SUBJECTS: Six healthy subjects (27-48 years old, two females) and two subjects with acute low back pain (46 and 65 years old females, one with diabetes/obesity). FIELD STRENGTH/SEQUENCE: 3-T, MR perfusion sequence. ASSESSMENT: Lumbar spines of healthy subjects were imaged axially at L3 level with a tag-on and tag-off alternating inversion recovery arterial spin labeling technique that suppresses background signal and acquires signal increase ratio (SIR) from the in-flow blood at varying inversion times (TI) from 0.12 seconds to 3.5 seconds. SIR vs. TI data were fit to determine the perfusion metrics of peak height (PH), time to peak (TTP), mean transit time, apparent muscle blood volume (MBV), and apparent muscle blood flow (MBF) in iliocostal, longissimus, and multifidus. Imaging was repeated immediately after healthy subjects performed a 20-minute walk, to determine the effect of exercise. STATISTICAL TESTS: Repeated measures analysis of variance. RESULTS: SIR vs. TI data showed well-defined leading and trailing edges, with sharply increasing SIR to TI of approximately 500 msec subsiding quickly to near zero around TI of 1500 msec. After exercise, the mean SIR at every TI increased markedly, resulting in significantly higher PH, MBV, and MBF (each P < 0.001 and F > 28.9), and a lower TTP (P < 0.05, F = 4.5), regardless of the muscle. MBF increased 2- to 2.5-fold after exercise, similar to the expected increase in cardiac output, given the intensity of the exercise. DATA CONCLUSIONS: Feasibility of an MR perfusion technique for muscle perfusion imaging was demonstrated, successfully detecting significantly increased perfusion after exercise. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Time-dependent inhibition of CYP3A4-mediated midazolam metabolism by macrolide antibiotics in CYP3A4 genetic variants: Comparison with testosterone metabolism.

OBJECTIVES: The present study aimed to evaluate the effects of CYP3A4 genetic variation on the kinetics of mechanism-based inhibition (MBI) of both inhibitors using midazolam as a substrate for comparison with our previous study, as midazolam and testosterone have different binding sites. BACKGROUND: The genetic variation of cytochrome P450 (CYP) 3A4 affects MBI, expressed as the maximum inactivation rate constant (kinact,max) and the inhibitor concentration required to achieve half-maximal inactivation (KI). We previously showed, using testosterone as a substrate, that the MBI kinetics of erythromycin and clarithromycin differ among CYP3A4 variants. MATERIALS AND METHODS: Midazolam 1'-hydroxylation inactivation profiles of erythromycin and clarithromycin were assessed using recombinant CYP3A4.1, .2, .7, .16, and .18 expressed in Escherichia coli. MBI parameters were calculated from changes in the inactivation rate constant (Δkobs) by the inhibitors. RESULTS: Both inhibitors increased Δkobs value in a concentration- and preincubation time-dependent manner, and MBI kinetics differed among variants. Trends of differences in MBI parameters among variants were similar to those assessed using testosterone as a substrate; KI decreased for CYP3A4.7, and kinact,max decreased for CYP3A4.2, .7, and .16. CONCLUSION: The genetic variation of recombinant CYP3A4 affects the MBI profile of CYP3A4 by erythromycin and clarithromycin, while the influence of genetic variation was similarly observed regardless of substrates. Our findings are of clinical relevance because the residual enzyme activity of CYP3A4 in the presence of inhibitor was estimated to vary among genetic variants.

Comparison of the inhibitory effects of azole antifungals on cytochrome P450 3A4 genetic variants.

Cytochrome P450 (CYP) 3A4 is one of the major drug-metabolizing enzymes. Genetic variants of CYP3A4 with altered activity are one of the factors responsible for interindividual differences in drug metabolism. Azole antifungals inhibit CYP3A4 to cause clinically significant drug-drug interactions. In the present quantitative study, we investigated the inhibitory effects of three azole antifungals (ketoconazole, voriconazole, and fluconazole) on testosterone metabolism by recombinant CYP3A4 genetic variants (CYP3A4.1 (WT), CYP3A4.2, CYP3A4.7, CYP3A4.16, and CYP3A4.18) and compared them with those previously reported for itraconazole. The inhibition constants (Ki) of ketoconazole, voriconazole, and fluconazole for rCYP3A4.1 were 3.6 nM, 3.2 µM, and 16.1 µM, respectively. The Ki values of these azoles for rCYP3A4.16 were 13.9-, 13.6-, and 6.2-fold higher than those for rCYP3A4.1, respectively, whereas the Ki value of itraconazole for rCYP3A4.16 was 0.54-fold of that for rCYP3A4.1. The other genetic variants had similar effects on the Ki values of the three azoles, whereas a very different pattern was seen for itraconazole. In conclusion, itraconazole has unique characteristics that are distinct from those shared by the other azole anti-fungal drugs ketoconazole, voriconazole, and fluconazole with regard to the influence of genetic variations on the inhibition of CYP3A4.

Ultrashort echo time time-spatial labeling inversion pulse magnetic resonance angiography with denoising deep learning reconstruction for the assessment of abdominal visceral arteries.

Current contrast-enhanced magnetic resonance angiography (MRA) and non-contrast-enhanced balanced steady-state free precession (bSSFP) MRA cause susceptibility artifacts from metallic devices in assessing endovascular visceral-artery interventions. The aims of this study are to investigate and compare image quality (IQ) and susceptibility artifacts of three-dimensional (3D) ultrashort echo time (UTE) time-spatial labeling inversion pulse (Time-SLIP) with those of 3D bSSFP Time-SLIP and to assess denoising deep learning reconstruction (dDLR) for the improvement of the signal-to-noise ratio (SNR) in 3D UTE with sparse sampling in phantoms and human subjects. This is a prospective type of study. Pulsatile glycerin-water flow phantom with platinum-tungsten-alloy coil, stainless-steel, nitinol, and cobalt-alloy stents were used. Ten healthy volunteers (seven males) and three patients (two males) were included in this study. 3D UTE Time-SLIP and 3D bSSFP Time-SLIP at 3T were used. The phantom-based study compared the signal-intensity ratio of the device levels (SRdevice ) and distal segments (SRdistal ) to the proximal segments. The volunteer-based study measured SNR, contrast ratio (CR), and IQ. The patient study evaluated local artifacts from metallic devices. Statistical tests included paired t-tests, Wilcoxon-signed rank tests, and Kruskal-Wallis tests. In the phantom-based study, SRdevice was small with UTE Time-SLIP, except the stainless-steel stent. SRdistal was greater (49.1%-90.4%) on bSSFP images than UTE images (-11.1% to 9.6%). Among volunteers, dDLR in UTE images improved SNR (p < 0.05) and IQ (p < 0.05), but CR was unaffected. UTE Time-SLIP showed inferior SNR and IQ than bSSFP Time-SLIP in images with and without dDLR (p < 0.05 for each). However, among patients, UTE Time-SLIP showed reduced metal artifacts compared to bSSFP Time-SLIP. Irrespective of the lower SNR and IQ of 3D UTE Time-SLIP than those of 3D bSSFP Time-SLIP, the former appeared to better depict flow after stenting or coiling. This indicates the potential of 3D UTE Time-SLIP to provide suitable diagnostic images of target vessels. dDLR improved SNR with reducing artifacts related to radial sampling, while maintaining the contrast. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

EID1 suppresses lipid accumulation by inhibiting the expression of GPDH in 3T3-L1 preadipocytes.

The imbalance between food intake and energy expenditure causes high accumulation of triglycerides in adipocytes. Obesity is related with the increased lipid accumulation in white adipose tissue, which is a major risk factor for the development of metabolic disorders, such as type 2 diabetes and cardiovascular disease. This study highlights the role of E1A-like inhibitor of differentiation 1 (EID1) in the modulation of adipogenesis through the downregulation of glycerol-3-phosphate dehydrogenase (GPDH), which is a key enzyme in the synthesis of triglycerides and is considered to be a marker of adipogenesis. By analyzing DNA microarray data, we found that when EID1 is overexpressed in preadipocytes (3T3-L1 cells) during adipocyte differentiation, EID1 inhibits lipid accumulation through the downregulation of GPDH. In contrast, EID1 is not involved in the regulation of intracellular glucose via the translocation of glucose transporter. A confocal image analysis showed that EID1 is located in the nucleus of preadipocytes in the form of speckles, which could be involved as a regulator of the transcriptional process. We further confirmed that EID1 is able to bind to the promoter sequence of GPDH in the nucleus. These findings provide a molecular explanation for the inhibitory effect of EID1 on lipid accumulation in adipocytes.

Comparison of axial and coronal acquisitions by non-contrast-enhanced renal 3D MR angiography using flow-in time-spatial labeling inversion pulse.

OBJECTIVE: We evaluated image quality differences between axial and coronal non-contrast-enhanced renal three-dimensional (3D) magnetic resonance angiography (MRA) acquisitions, using time-spatial labeling inversion pulse (Time-SLIP) with flow-in balanced steady-state free precession (bSSFP). MATERIALS AND METHODS: Axial and coronal images were acquired in 128 subjects using non-contrast-enhanced 3D-MRA with Time-SLIP flow-in bSSFP on a clinical 1.5-T MRI system. Visualization of source and maximum intensity projection (MIP) images of renal arteries were compared between the axial and coronal acquisitions using a four-point scale. For quantitative analysis, vessel-to-background contrast ratios of aorta and renal arteries were calculated. RESULTS: Both acquisitions yielded similarly excellent quality. In source image evaluation, coronal acquisitions showed significantly more motion degradation (p < 0.01) than did axial acquisitions. In MIP image evaluation, coronal acquisitions yielded superior image quality, less motion degradation, and better visualization of the number of renal branches than did axial acquisition. The renal artery to background signal contrast was greater in coronal than in axial acquisitions (p < 0.01). CONCLUSION: Coronal acquisition provides superior contrast between the renal arteries and background and allows more persistent visualization than axial acquisitions in non-contrast-enhanced MRA using flow-in bSSFP with Time-SLIP. First-line screening of renal non-contrast-enhanced MRA should involve coronal acquisition.

L-Lactate dehydrogenase B may be a predictive marker for sensitivity to anti-EGFR monoclonal antibodies in colorectal cancer cell lines.

Recently, proteins derived from cancer cells have been widely investigated as biomarkers for predicting the efficacy of chemotherapy. In this study, to identify a sensitive biomarker for the efficacy of anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs), proteins derived from 6 colorectal cancer (CRC) cell lines with different sensitivities to cetuximab, an anti-EGFR mAb, were analyzed. Cytoplasmic and membrane proteins extracted from each CRC cell line were digested using trypsin and analyzed comprehensively using mass spectrometry. As a result, 148 and 146 peaks from cytoplasmic proteins and 363 and 267 peaks from membrane proteins were extracted as specific peaks for cetuximab-resistant and -sensitive CRC cell lines, respectively. By analyzing the proteins identified from the peptide peaks, cytoplasmic L-lactate dehydrogenase B (LDHB) was detected as a marker of cetuximab sensitivity, and it was confirmed that LDHB expression was increased in cetuximab-resistant CRC cell lines. Furthermore, LDHB expression levels were significantly upregulated with the acquisition of resistance to cetuximab in cetuximab-sensitive CRC cell lines. In conclusion, LDHB was identified as an important factor affecting cetuximab sensitivity using comprehensive proteome analysis for the first time.

B1 Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain.

The chemical exchange saturation transfer (CEST) effect on an egg white (EW) suspension was investigated for optimization of magnetization transfer (MT) power (B1,rms) and pH dependency with the addition of lactic acid. Applying a higher MT pulse, B1,rms, Z-spectrum shows higher asymmetry and the magnetisation transfer ratio (MTR)asym signal increases to around 1-3.5 ppm, indicating a higher CEST effect. Amide proton transfer (APT) at 3.5 ppm shows a signal elevation in MTRasym with the application of higher B1,rms power and high pH. In addition, the hydroxyl proton signal in MTRasym increases as pH is reduced by lactic acid. In Z-spectrum of B1,rms at 1.0 µT and 2.0 µT, the dependence on CEST effect of amide proton and hydroxyl proton could be observed by using an EW suspension phantom. The CEST MT power was optimized on the EW suspension phantom with pH dependency and further confirmed on volunteers. In addition, APT imaging at 3.5 ppm using B1,rms at 1.0 µT performed on two human brains with different pathophysiological conditions indicated appropriate ATP effect.

Amide proton transfer-weighted imaging to differentiate malignant from benign pulmonary lesions: Comparison with diffusion-weighted imaging and FDG-PET/CT.

PURPOSE: To compare the capability of amide proton transfer-weighted (APTw) imaging, diffusion-weighted imaging (DWI), and FDG-PET/CT for the differentiation of malignant from benign pulmonary nodules. MATERIALS AND METHODS: In all, 82 consecutive patients with pulmonary nodules underwent APTw imaging and DWI with a 3T system, and FDG-PET/CT. All nodules were divided as either malignant (n = 49) or benign (n = 39) groups based on pathological and follow-up examinations. To evaluate the capability for differentiation of malignant from benign nodules, magnetization transfer ratio asymmetry (MTRasym )(3.5ppm) on APTw imaging, apparent diffusion coefficient (ADC), and maximum value of standard uptake value (SUVmax ) were assessed. Receiver operating characteristic (ROC) analyses were performed to computationally determine each feasible threshold value. Next, McNemar's test was used for comparing diagnostic performance with each other as well as with a combination of the significant factors determined by multivariate logistic regression analysis. RESULTS: Although sensitivity of ADC was significantly higher than that of MTRasym (3.5 ppm) (P = 0.002) and SUVmax (P = 0.004), specificity of MTRasym (3.5 ppm) and SUVmax was significantly higher than that of ADC (P < 0.05). Sensitivity of combined MTRasym (3.5ppm) with SUVmax was significantly higher than that of MTRasym (3.5ppm) (P = 0.001) and SUVmax (P = 0.002) alone. Moreover, specificity and accuracy of combined MTRasym (3.5ppm) with SUVmax were significantly higher than that of ADC (specificity: P = 0.002, accuracy: P = 0.008). CONCLUSION: APTw imaging appears to be as useful as DWI and FDG-PET/CT for differentiation of malignant from benign nodules. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1013-1021.

Standard-, Reduced-, and No-Dose Thin-Section Radiologic Examinations: Comparison of Capability for Nodule Detection and Nodule Type Assessment in Patients Suspected of Having Pulmonary Nodules.

Purpose To compare the capability of pulmonary thin-section magnetic resonance (MR) imaging with ultrashort echo time (UTE) with that of standard- and reduced-dose thin-section computed tomography (CT) in nodule detection and evaluation of nodule type. Materials and Methods The institutional review board approved this study, and written informed consent was obtained from each patient. Standard- and reduced-dose chest CT (60 and 250 mA) and MR imaging with UTE were used to examine 52 patients; 29 were men (mean age, 66.4 years ± 7.3 [standard deviation]; age range, 48-79 years) and 23 were women (mean age, 64.8 years ± 10.1; age range, 42-83 years). Probability of nodule presence was assessed for all methods with a five-point visual scoring system. All nodules were then classified as missed, ground-glass, part-solid, or solid nodules. To compare nodule detection capability of the three methods, consensus for performances was rated by using jackknife free-response receiver operating characteristic analysis, and κ analysis was used to compare intermethod agreement for nodule type classification. Results There was no significant difference (F = 0.70, P = .59) in figure of merit between methods (standard-dose CT, 0.86; reduced-dose CT, 0.84; MR imaging with UTE, 0.86). There was no significant difference in sensitivity between methods (standard-dose CT vs reduced-dose CT, P = .50; standard-dose CT vs MR imaging with UTE, P = .50; reduced-dose CT vs MR imaging with UTE, P >.99). Intermethod agreement was excellent (standard-dose CT vs reduced-dose CT, κ = 0.98, P < .001; standard-dose CT vs MR imaging with UTE, κ = 0.98, P < .001; reduced-dose CT vs MR imaging with UTE, κ = 0.99, P < .001). Conclusion Pulmonary thin-section MR imaging with UTE was useful in nodule detection and evaluation of nodule type, and it is considered at least as efficacious as standard- or reduced-dose thin-section CT. © RSNA, 2017 Online supplemental material is available for this article.

Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages.

Tunneling nanotubes (TNTs), the long membrane extensions connecting distant cells, have emerged as a novel form of cell-to-cell communication. However, it is not fully understood how and to what extent TNTs contribute to intercellular spread of pathogens including HIV-1. In this study, we show that HIV-1 promotes TNT formation per se via its protein Nef and a cellular protein M-Sec, which appears to mediate approximately half of viral spread among monocyte-derived macrophages (MDMs). A small compound that inhibits M-Sec-induced TNT formation reduced HIV-1 production by almost half in MDMs. Such inhibition was not observed with Nef-deficient mutant HIV-1 that fails to promote TNT formation and replicates less efficiently than the wild-type HIV-1 in MDMs. The TNT inhibitor-sensitive/Nef-promoting viral production was also observed in a T cell line ectopically expressing M-Sec, but not in another M-Sec(-) T cell line. Our results suggest the importance of TNTs in HIV-1 spread among MDMs and might answer the long-standing question how Nef promotes HIV-1 production in a cell type-specific manner.