Twin Robotic X-Ray System for 3D Cone-Beam CT of the Wrist: An Evaluation of Image Quality and Radiation Dose.

OBJECTIVE. The purpose of this study was to assess image quality and radiation dose of a novel twin robotic x-ray system's 3D cone-beam CT (CBCT) function for the depiction of cadaveric wrists. MATERIALS AND METHODS. Sixteen cadaveric wrists were scanned using dedicated low-dose and standard-dose CBCT protocols as well as clinical MDCT for comparison. Three readers assessed overall image quality, noise, and artifacts in bone and soft tissue on 5-point Likert scales. For radiation dose analysis, volume CT dose indexes (CTDIvol) were compared. RESULTS. Overall image quality of most studies was very good or excellent in MDCT (for readers 1, 2, and 3: 100%, 100%, and 88%, respectively), standard-dose CBCT (100%, 100%, and 94%), and low dose CBCT (100%, 94%, and 88%) with two readers favoring standard-dose CBCT over MDCT image quality (readers 1 and 2; p ≤ 0.046). In soft tissue, standard-dose (readers 1, 2, and 3; p ≤ 0.021) and low-dose (all p ≤ 0.001) CBCT images had more noise than MDCT in all cases. Standard-dose (all p ≤ 0.003) and low-dose (all p < 0.001) CBCT images also displayed more artifacts. In osseous tissue, one reader observed more noise (p < 0.001) and artifacts (p = 0.020) for low-dose CBCT than for MDCT, whereas no difference was found between standard-dose CBCT and MDCT. Mean CTDIvol was significantly lower for standard-dose (5.2 ± 0.6 mGy; p < 0.001) and low-dose CBCT (1.8 ± 0.2 mGy; p < 0.001) than for clinical MDCT without automatic dose modulation (15.0 ± 0.0 mGy). CONCLUSION. The tested CBCT function delivers suitable image quality for clinical wrist imaging at significantly lower radiation levels than conventional MDCT. In combination with comfortable positioning options and the ability to perform additional radiographic and fluoroscopic examinations, the twin robotic x-ray system may hold the potential to be a one-stop shop device for trauma-associated wrist imaging.

A Modified Tripeptide Motif of RS1 (RSC1A1) Down-Regulates Exocytotic Pathways of Human Na+-d-glucose Cotransporters SGLT1, SGLT2, and Glucose Sensor SGLT3 in the Presence of Glucose.

A domain of protein RS1 (RSC1A1) called RS1-Reg down-regulates the plasma membrane abundance of Na+-d-glucose cotransporter SGLT1 by blocking the exocytotic pathway at the trans-Golgi. This effect is blunted by intracellular glucose but prevails when serine in a QSP (Gln-Ser-Pro) motif is replaced by glutamate [RS1-Reg(S20E)]. RS1-Reg binds to ornithine decarboxylase (ODC) and inhibits ODC in a glucose-dependent manner. Because the ODC inhibitor difluoromethylornithine (DFMO) acts like RS1-Reg(S20E), and DFMO and RS1-Reg(S20E) are not cumulative, we raised the hypothesis that RS1-Reg(S20E) down-regulates the exocytotic pathway of SGLT1 at the trans-Golgi by inhibiting ODC. We investigated whether QEP down-regulates human SGLT1 (hSGLT1) like hRS1-Reg(S20E) and whether human Na+-d-glucose cotransporter hSGLT2 and the human glucose sensor hSGLT3 are also addressed. We expressed hSGLT1, hSGLT1 linked to yellow fluorescent protein (hSGLT1-YFP), hSGLT2-YFP and hSGLT3-YFP in oocytes of Xenopus laevis, injected hRS1-Reg(S20E), QEP, DFMO, and/or α-methyl-d-glucopyranoside (AMG), and measured AMG uptake, glucose-induced currents, and plasma membrane-associated fluorescence after 1 hour. We also performed in vitro AMG uptake measurements into small intestinal mucosa of mice and human. The data indicate that QEP down-regulates the exocytotic pathway of SGLT1 similar to hRS1-Reg(S20E). Our results suggests that both peptides also down-regulate hSGLT2 and hSGLT3 via the same pathway. Thirty minutes after application of 5 mM QEP in the presence of 5 mM d-glucose, hSGLT1-mediated AMG uptake into small intestinal mucosa was decreased by 40% to 50%. Thus oral application of QEP in a formulation that optimizes uptake into enterocytes but prevents entry into the blood is proposed as novel antidiabetic therapy.

Phosphorylation of RS1 (RSC1A1) Steers Inhibition of Different Exocytotic Pathways for Glucose Transporter SGLT1 and Nucleoside Transporter CNT1, and an RS1-Derived Peptide Inhibits Glucose Absorption.

Cellular uptake adapts rapidly to physiologic demands by changing transporter abundance in the plasma membrane. The human gene RSC1A1 codes for a 67-kDa protein named RS1 that has been shown to induce downregulation of the sodium-D-glucose cotransporter 1 (SGLT1) and of the concentrative nucleoside transporter 1 (CNT1) in the plasma membrane by blocking exocytosis at the Golgi. Injecting RS1 fragments into Xenopus laevis oocytes expressing SGLT1 or CNT1 and measuring the expressed uptake of α-methylglucoside or uridine 1 hour later, we identified a RS1 domain (RS1-Reg) containing multiple predicted phosphorylation sites that is responsible for this post-translational downregulation of SGLT1 and CNT1. Dependent on phosphorylation, RS1-Reg blocks the release of SGLT1-containing vesicles from the Golgi in a glucose-dependent manner or glucose-independent release of CNT1-containing vesicles. We showed that upregulation of SGLT1 in the small intestine after glucose ingestion is promoted by glucose-dependent disinhibition of the RS1-Reg-blocked exocytotic pathway of SGLT1 between meals. Mimicking phosphorylation of RS1-Reg, we obtained a RS1-Reg variant that downregulates SGLT1 in the brush-border membrane at high luminal glucose concentration. Because RS1 mediates short-term regulation of various transporters, we propose that the RS1-Reg-navigated transporter release from Golgi represents a basic regulatory mechanism of general importance, which implies the existence of receptor proteins that recognize different phosphorylated forms of RS1-Reg and of complex transporter-specific sorting in the trans-Golgi. RS1-Reg-derived peptides that downregulate SGLT1 at high intracellular glucose concentrations may be used for downregulation of glucose absorption in small intestine, which has been proposed as strategy for treatment of type 2 diabetes.

Protein RS1 (RSC1A1) Downregulates the Exocytotic Pathway of Glucose Transporter SGLT1 at Low Intracellular Glucose via Inhibition of Ornithine Decarboxylase.

Na+-d-glucose cotransporter 1 (SGLT1) is rate-limiting for glucose absorption in the small intestine. Shortly after intake of glucose-rich food, SGLT1 abundance in the luminal membrane of the small intestine is increased. This upregulation occurs via glucose-induced acceleration of the release of SGLT1-containing vesicles from the trans-Golgi network (TGN), which is regulated by a domain of protein RS1 (RSC1A1) named RS1-Reg. Dependent on phosphorylation, RS1-Reg blocks release of vesicles containing SGLT1 or concentrative nucleoside transporter 1. The hypothesis has been raised that RS1-Reg binds to different receptor proteins at the TGN, which trigger release of vesicles with different transporters. To identify the presumed receptor proteins, two-hybrid screening was performed. Interaction with ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme of polyamine synthesis, was observed and verified by immunoprecipitation. Binding of RS1-Reg mutants to ODC1 was characterized using surface plasmon resonance. Inhibition of ODC1 activity by RS1-Reg mutants and the ODC1 inhibitor difluoromethylornithine (DFMO) was measured in the absence and presence of glucose. In addition, short-term effects of DFMO, RS1-Reg mutants, the ODC1 product putrescine, and/or glucose on SGLT1 expressed in oocytes of Xenopus laevis were investigated. High-affinity binding of RS1-Reg to ODC1 was demonstrated, and evidence for a glucose binding site in ODC1 was provided. Binding of RS1-Reg to ODC1 inhibits the enzymatic activity at low intracellular glucose, which is blunted at high intracellular glucose. The data suggest that generation of putrescine by ODC1 at the TGN stimulates release of SGLT1-containing vesicles. This indicates a biomedically important role of ODC1 in regulation of glucose homeostasis.

Evaluation of Ultra-High-Resolution Cone-Beam CT Prototype of Twin Robotic Radiography System for Cadaveric Wrist Imaging.

RATIONALE AND OBJECTIVES: Cone-beam CT (CBCT) applications possess potential for dose reduction in musculoskeletal imaging. This study evaluates the ultra-high-resolution CBCT prototype of a twin robotic X-ray system in wrist examinations compared to high-resolution multidetector CT (MDCT). MATERIALS AND METHODS: Sixteen wrists of body donors were examined with the CBCT scan mode and a 384 slice MDCT system. Radiation-equivalent low-dose (CTDIvol(16cm)  = 3.3 mGy) and full-dose protocols (CTDIvol(16cm)  = 13.8 mGy) were used for both systems. Two observers assessed image quality on a seven-point Likert scale. In addition, software-assisted quantification of signal intensity fractions in cancellous bone was performed. Fewer pixels with intermediate signal intensity were considered to indicate superior depiction of bone microarchitecture. RESULTS: Subjective image quality in CBCT was superior to dose equivalent MDCT with p ≤ 0.03 for full-dose and p < 0.001 for low-dose scans, respectively. Median Likert values were 7/7 (reader 1 / reader 2) in full-dose CBCT, 6/6 in full-dose MDCT, 5/6 in low-dose CBCT and 3/3 in low-dose MDCT. Intraclass correlation coefficient was 0.936 (95% confidence interval, 0.897-0.961; p < 0.001), indicating excellent reliability. Objective analysis displayed smaller fractions of "indecisive" pixels with intermediate signal intensity for full-dose CBCT (0.57 [interquartile range 0.13]) compared to full-dose MDCT (0.68 [0.21]), low-dose CBCT (0.72 [0.19]), and low-dose MDCT (0.80 [0.15]) studies. No significant difference was observed between low-dose CBCT and full-dose MDCT. CONCLUSION: The new CBCT prototype provides superior image quality for trabecula and bone marrow in cadaveric wrist studies and enables dose reduction up to 75% compared to high-resolution MDCT.

3D cone-beam CT with a twin robotic x-ray system in elbow imaging: comparison of image quality to high-resolution multidetector CT.

BACKGROUND: Elbow imaging is challenging with conventional multidetector computed tomography (MDCT), while cone-beam CT (CBCT) provides superior options. We compared intra-individually CBCT versus MDCT image quality in cadaveric elbows. METHODS: A twin robotic x-ray system with new CBCT mode and a high-resolution clinical MDCT were compared in 16 cadaveric elbows. Both systems were operated with a dedicated low-dose (LD) protocol (equivalent volume CT dose index [CTDIvol(16 cm)] = 3.3 mGy) and a regular clinical scan dose (RD) protocol (CTDIvol(16 cm) = 13.8 mGy). Image quality was evaluated by two radiologists (R1 and R2) on a seven-point Likert scale, and estimation of signal intensity in cancellous bone was conducted. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) statistics were used. RESULTS: The CBCT prototype provided superior subjective image quality compared to MDCT scans (for RD, p ≤ 0.004; for LD, p ≤ 0.001). Image quality was rated very good or excellent in 100% of the cases by both readers for RD CBCT, 100% (R1) and 93.8% (R2) for LD CBCT, 62.6% and 43.8% for RD MDCT, and 0.0% and 0.0% for LD MDCT. Single-measure ICC was 0.95 (95% confidence interval 0.91-0.97; p < 0.001). Software-based assessment supported subjective findings with less "undecided" pixels in CBCT than dose-equivalent MDCT (p < 0.001). No significant difference was found between LD CBCT and RD MDCT. CONCLUSIONS: In cadaveric elbow studies, the tested cone-beam CT prototype delivered superior image quality compared to high-end multidetector CT and showed a potential for considerable dose reduction.

3D cone-beam CT of the ankle using a novel twin robotic X-ray system: Assessment of image quality and radiation dose.

PURPOSE: To evaluate image quality (IQ) and radiation dose in cone-beam computed tomography (CBCT) of the ankle using a novel twin robotic X-ray system. METHOD: We examined 16 cadaveric ankles with standard-dose (FD) and low-dose (LD) protocols using the new system's CBCT mode. For comparison, we performed multi-slice CT imaging (MSCT) with a clinical protocol. Three radiologists assessed IQ, noise and artifacts in bone and soft tissue on a five-point Likert scale (1= poor IQ; strong noise or artifacts; 5= excellent IQ; minimal noise or artifacts). Volume CT dose indices (CTDIvol) were calculated for radiation dose comparison between CBCT and MSCT. RESULTS: Overall IQ was described as very good or excellent by reader 1/2/3 in 62.5/87.5/56.3% of LD, 87.5/87.5/81.3% of FD and 100/87.5/87.5% of MSCT studies. Readers agreed that IQ was better in MSCT than LD (R1/R2/R3; p ≤ 0.008), two also found advantages of MSCT over FD (R1/R3; p ≤ 0.034). Soft tissue noise and artifacts were stronger in FD (all p ≤ 0.002) and LD (all p ≤ 0.001). In bone, artifacts and noise were also more severe in LD (all p < 0.001) and FD (all p ≤ 0.003). CTDIvol for clinical MSCT scans without dose modulation (15.0 ± 0.0 mGy) were higher than for FD (5.3 ± 1.0 mGy) and LD studies (2.9 ± 0.6 mGy; both p < 0.001). CONCLUSIONS: Despite MSCT providing better overall IQ than the twin robotic X-ray system's CBCT mode, both cone-beam protocols offer very good IQ in most studies and are suitable for clinical ankle imaging. Standard-dose and especially low-dose CBCT studies deliver up to five times less radiation dose than MSCT imaging.

In vitro evaluation of a new iterative reconstruction algorithm for dose reduction in coronary artery calcium scoring.

BACKGROUND: Coronary artery calcium (CAC) scoring is a widespread tool for cardiac risk assessment in asymptomatic patients and accompanying possible adverse effects, i.e. radiation exposure, should be as low as reasonably achievable. PURPOSE: To evaluate a new iterative reconstruction (IR) algorithm for dose reduction of in vitro coronary artery calcium scoring at different tube currents. MATERIAL AND METHODS: An anthropomorphic calcium scoring phantom was scanned in different configurations simulating slim, average-sized, and large patients. A standard calcium scoring protocol was performed on a third-generation dual-source CT at 120 kVp tube voltage. Reference tube current was 80 mAs as standard and stepwise reduced to 60, 40, 20, and 10 mAs. Images were reconstructed with weighted filtered back projection (wFBP) and a new version of an established IR kernel at different strength levels. Calcifications were quantified calculating Agatston and volume scores. Subjective image quality was visualized with scans of an ex vivo human heart. RESULTS: In general, Agatston and volume scores remained relatively stable between 80 and 40 mAs and increased at lower tube currents, particularly in the medium and large phantom. IR reduced this effect, as both Agatston and volume scores decreased with increasing levels of IR compared to wFBP (P < 0.001). Depending on selected parameters, radiation dose could be lowered by up to 86% in the large size phantom when selecting a reference tube current of 10 mAs with resulting Agatston levels close to the reference settings. CONCLUSION: New iterative reconstruction kernels may allow for reduction in tube current for established Agatston scoring protocols and consequently for substantial reduction in radiation exposure.

Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion.

To clarify the physiological role of Na(+)-D-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(-/-) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(-/-) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(-/-) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose-free diet. In wild-type mice, passage of D-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(-/-) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2.