Noninvasive skin fluorescence spectroscopy for detection of abnormal glucose tolerance.

The ENGINE study evaluated noninvasive skin fluorescence spectroscopy (SFS) for detection of abnormal glucose tolerance (AGT). The AGT detection performance of SFS was compared to fasting plasma glucose (FPG) and hemoglobin A1C (A1C). The study was a head-to-head comparison of SFS to FPG and A1C in an at-risk population of 507 subjects, with no prior diagnosis of diabetes, each of whom received a 75 g, two-hour oral glucose tolerance test (OGTT). Subjects were measured by SFS on multiple days in fasting and non-fasting states. SFS data were acquired and analyzed with the SCOUT DS® device (VeraLight, Albuquerque, NM, USA). Disease truth was AGT, defined as OGTT ≥ 7.8 mmol/L. Sensitivity, false positive rate (FPR), ROC area, and equal error rate (EER) for detection of AGT were computed. The reproducibility of SFS and FPG was assessed. The AGT sensitivity of SFS at the device's recommended screening threshold of 50 was 75.2%, higher than that of FPG (thresholds of 5.6 mmol/L or 6.1 mmol/L) and A1C (thresholds of 5.7% or 6.0%). The SFS FPR was 42.1%, comparable to an A1C threshold of 5.7% (FPR = 43.5%). The EERs of SFS, FPG and A1C were similar, as were the partial ROC areas for FPRs of 20-50%. The reproducibility of SFS was 7.7% versus 8.1% for FPG. SFS had similar AGT detection performance to FPG and A1C and is a viable alternative to screening individuals for AGT.

Noninvasive skin fluorescence spectroscopy is comparable to hemoglobin A1c and fasting plasma glucose for detection of abnormal glucose tolerance.

AIM: We compare performance of noninvasive skin fluorescence spectroscopy (SFS), fasting plasma glucose (FPG), and hemoglobin A1c (A1C) for detection of abnormal glucose tolerance (AGT). METHODS: The NSEEDS trial evaluated SFS, FPG, and A1C in an at-risk population of 479 previously undiagnosed subjects from nine US centers, each of whom received a 75 g, 2 h oral glucose tolerance test (OGTT). Skin fluorescence spectra were collected and analyzed with SCOUT DS® devices. Disease truth was AGT, defined as OGTT ≥140 mg/dl. Abnormal glucose tolerance sensitivity, false positive rate (FPR), and receiver operating characteristic (ROC) curves were computed for each measurement technique. Skin fluorescence spectroscopy reproducibility was also assessed. RESULTS: The AGT sensitivity of SFS was 68.2%, higher than that of FPG (thresholds of 100 and 110 mg/dl) and A1C (thresholds of 5.7% and 6.0%). The FPR of SFS was 37.7%, comparable to A1C at the 5.7% threshold (30.7%). Partial ROC areas of SFS, FPG, and A1C were similar for FPRs of 20-50% (average sensitivities of 64.0%, 59.0%, and 68.6%, respectively). The interday coefficient of variation for SFS was 7.6%. CONCLUSIONS: Skin fluorescence spectroscopy has similar screening performance to FPG and A1C and is a viable approach for detection of AGT.

Cross-sectional evaluation of noninvasively detected skin intrinsic fluorescence and mean hemoglobin a1c in type 1 diabetes.

BACKGROUND: This study evaluated the relationship between skin intrinsic fluorescence (SIF) and long-term mean hemoglobin A1c (HbA1c) in individuals with type 1 diabetes. SUBJECTS AND METHODS: We undertook a cross-sectional analysis of 172 individuals with type 1 diabetes followed longitudinally with HbA1c data available over an average of 16.6 years. SIF was evaluated cross-sectionally using the SCOUT DS device (VeraLight Inc., Albuquerque, NM) and correlated with most recent HbA1c and long-term mean HbA1c. Potential determinants of this relationship, including age, gender, smoking status, duration of diabetes, and renal function, were also evaluated. RESULTS: Age-adjusted skin intrinsic fluorescence significantly correlated with long-term mean HbA1c (R=0.44, P<0.0001). In contrast, there was no significant relationship between SIF and most recent HbA1c (R=0.14, P=0.075). The best-fit model describing the relationship between SIF and mean HbA1c controlled for factors of age, duration of disease, renal function, and site of study conduct. Controlling for these factors was also important in understanding the relationship between most recent HbA1c and SIF. Evaluating longer-term HbA1c data also strengthened the relationship between SIF and mean HbA1c. In the presence of renal dysfunction or damage, as indicated by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or presence of gross proteinuria, there was no significant correlation between SIF and mean HbA1c. CONCLUSIONS: Noninvasive detection of SIF significantly correlates with long-term mean HbA1c, providing insight into long-term glycemic exposure. Age, duration of diabetes, and renal function are potential contributors to this relationship.

Noninvasive type 2 diabetes screening: clinical evaluation of SCOUT DS in an Asian Indian cohort.

OBJECTIVE: This study evaluated the noninvasive, point-of-care diabetes screening device, Scout DS (VeraLight Inc., Albuquerque, NM) (SCOUT), in a native Asian Indian cohort. RESEARCH DESIGN AND METHODS: SCOUT is a tabletop, skin fluorescence spectrometer that reports a risk score following a 3-4-min noninvasive measurement of a subject's left volar forearm. SCOUT, fasting plasma glucose (FPG), and hemoglobin A(1c) (A1C) were compared for detection of abnormal glucose tolerance (AGT) in a cohort of 256 subjects without previous diagnosis of diabetes or impaired glucose tolerance in Chennai, India. After an overnight fast, a 75-g, 2-h oral glucose tolerance test was administered, and AGT was defined as a plasma glucose value ≥ 140 mg/dL (7.8 mmol/dL). Sensitivity, false-positive rate (FPR), and receiver-operating characteristics area under the curve for AGT detection were computed for SCOUT, FPG, and A1C. Intra-day reproducibility of SCOUT was assessed. RESULTS: SCOUT, FPG, and A1C (at respective thresholds of 50, 110 mg/dL, and 5.7%) exhibited sensitivities of 87%, 32%, and 86%, respectively, and FPR of 52%, 3%, and 58%, respectively. For the 177 subjects receiving a valid SCOUT Diabetes Score on both measurement attempts, the coefficient of variation was 5.8%, and the Pearson correlation was 0.91. A SCOUT score could be obtained on 91% of subjects after two attempts. CONCLUSIONS: The performance of SCOUT is similar to that of A1C, whereas FPG had a much lower sensitivity. SCOUT is an effective tool for AGT screening in Asian Indians.

Three-dimensional prepolarized magnetic resonance imaging using rapid acquisition with relaxation enhancement.

Prepolarized MRI (PMRI) with pulsed electromagnets has the potential to produce diagnostic quality 0.5- to 1.0-T images with significantly reduced cost, susceptibility artifacts, specific absorption rate, and gradient noise. In PMRI, the main magnetic field cycles between a high field (B(p)) to polarize the sample and a homogeneous, low field (B(0)) for data acquisition. This architecture combines the higher SNR of the polarizing field with the imaging benefits of the lower field. However, PMRI can only achieve high SNR efficiency for volumetric imaging with 3D rapid imaging techniques, such as rapid acquisition with relaxation enhancement (RARE) (FSE, TSE), because slice-interleaved acquisition and longitudinal magnetization storage are both inefficient in PMRI. This paper demonstrates the use of three techniques necessary to achieve efficient, artifact-free RARE in PMRI: quadratic nulling of concomitant gradient fields, electromotive force cancelation during field ramping, and phase compensation of CPMG echo trains. This paper also demonstrates the use of 3D RARE in PMRI to achieve standard T(1) and fat-suppressed T(2) contrast in phantoms and in vivo wrists. These images show strong potential for future clinical application of PMRI to extremity musculoskeletal imaging and peripheral angiography.

Prepolarized magnetic resonance imaging around metal orthopedic implants.

A prepolarized MRI (PMRI) scanner was used to image near metal implants in agar gel phantoms and in in vivo human wrists. Comparison images were made on 1.5- and 0.5-T conventional whole-body systems. The PMRI experiments were performed in a smaller bore system tailored to extremity imaging with a prepolarization magnetic field of 0.4 T and a readout magnetic field of 27-54 mT (1.1-2.2 MHz). Scan parameters were chosen with equal readout gradient strength over a given field of view and matrix size to allow unbiased evaluation of the benefits of lower readout frequency. Results exhibit substantial reduction in metal susceptibility artifacts under PMRI versus conventional scanners. A new artifact quantification technique is also presented, and phantom results confirm that susceptibility artifacts improve as expected with decreasing readout magnetic field using PMRI. This proof-of-concept study demonstrates that prepolarized techniques have the potential to provide diagnostic cross-sectional images for postoperative evaluation of patients with metal implants.

Magnetic resonance imaging with T1 dispersion contrast.

Prepolarized MRI uses pulsed magnetic fields to produce MR images by polarizing the sample at one field strength (approximately 0.5 T) before imaging at a much lower field (approximately 50 mT). Contrast reflecting the T(1) of the sample at an intermediate field strength is achieved by polarizing the sample and then allowing the magnetization to decay at a chosen "evolution" field before imaging. For tissues whose T(1) varies with field strength (T(1) dispersion), the difference between two images collected with different evolution fields yields an image with contrast reflecting the slope of the T(1) dispersion curve between those fields. Tissues with high protein content, such as muscle, exhibit rapid changes in their T(1) dispersion curves at 49 and 65 mT due to cross-relaxation with nitrogen nuclei in protein backbones. Tissues without protein, such as fat, have fairly constant T(1) over this range; subtracting images with two different evolution fields eliminates signal from flat T(1) dispersion species. T(1) dispersion protein-content images of the human wrist and foot are presented, showing clear differentiation between muscle and fat. This technique may prove useful for delineating regions of muscle tissue in the extremities of patients with diseases affecting muscle viability, such as diabetic neuropathy, and for visualizing the protein content of tissues in vivo.

Rapid polarizing field cycling in magnetic resonance imaging.

We describe the electronics for controlling the independently pulsed polarizing coil in a prepolarized magnetic resonance imaging (PMRI) system and demonstrate performance with free induction decay measurements and in vivo imaging experiments. A PMRI scanner retains all the benefits of acquiring MRI data at low field, but with the higher signal of the polarizing field. Rapidly and efficiently ramping the polarizing coil without disturbing the data acquisition is one of the major challenges of PMRI. With our modular hardware design, we successfully ramp the 0.4-T polarizing coil of a wrist-sized PMRI scanner at up to 100 T/s without causing image artifacts or otherwise degrading data acquisition.