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Background and Aims: Recent studies have unveiled an association between ADAMTS7 gene variation and coronary artery disease (CAD) caused by atherosclerosis. We investigated if the ADAMTS7 Serine214-to-Proline substitution arising from a CAD-associated variant affected angiogenesis, since neovascularization plays an important role in atherosclerosis. Methods and Results: ADAMTS7 knockdown in vascular endothelial cells (ECs) attenuated their angiogenesis potential, whereas augmented ADAMTS7-Ser214 expression had the opposite effect, leading to increased ECs migratory and tube formation ability. Proteomics analysis showed an increase in thrombospondin-1, a reported angiogenesis inhibitor, in culture media conditioned by ECs with ADAMTS7 knockdown and a decrease of thrombospondin-1 in media conditioned by ECs with ADAMTS7-Ser214 overexpression. Cleavage assay indicated that ADAMTS7 possessed thrombospondin-1 degrading activity, which was reduced by the Ser214-to-Pro substitution. The pro-angiogenic effect of ADAMTS7-Ser214 diminished in the presence of a thrombospondin-1 blocking antibody. Conclusions: The ADAMTS7 Ser217-to-Pro substitution as a result of ADAMTS7 polymorphism affects thrombospondin-1 degradation, thereby promoting atherogenesis through increased EC migration and tube formation.

Increasingly, safety-critical systems include artificial intelligence and machine learning components (i.e., Learning-Enabled Components (LECs)). However, when behavior is learned in a training environment that fails to fully capture real-world phenomena, the response of an LEC to untrained phenomena is uncertain, and therefore cannot be assured as safe. Automated methods are needed for self-assessment and adaptation to decide when learned behavior can be trusted. This work introduces a model-driven approach to manage self-adaptation of a Learning-Enabled System (LES) to account for run-time contexts for which the learned behavior of LECs cannot be trusted. The resulting framework enables an LES to monitor and evaluate goal models at run time to determine whether or not LECs can be expected to meet functional objectives. Using this framework enables stakeholders to have more confidence that LECs are used only in contexts comparable to those validated at design time.

Background and objectives Recent studies have demonstrated that near-infrared (IR) imaging can be used to acquire high-contrast images of root caries and calculus on the root surfaces of extracted teeth at wavelengths longer than 1450 nm. The purpose of this study was to determine if image-guided laser ablation can be used to selectively remove calculus from tooth surfaces with minimal damage to the underlying sound cementum and dentin. Materials and methods In this study, sequential near-IR images at 1500-1700 nm were used to guide a diode-pumped (DPSS) Er:YAG laser for the removal of calculus from the root surfaces of 10 extracted teeth. The selectivity of removal was assessed using digital microscopy, optical coherence tomography, and surface profilometry. Results Calculus was removed rapidly with minimal damage to the underlying sound cementum and dentin. Image-guided ablation achieved high-selectivity, the mean volume of calculus removal was more than 27 times higher than the mean loss of cementum. Conclusions We have demonstrated that near-IR image-guided laser ablation can be used for the selective removal of calculus from root surfaces ex vivo. Additionally, we have demonstrated that a diode-pumped solid-state Er:YAG laser is well suited for selective removal. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Background Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown. Methods We assessed LA size, function, and deformation on cardiovascular magnetic resonance (CMR) in 238 genotyped HCM patients and compared this with twenty age, sex, blood pressure and body mass index matched control subjects. We further evaluated the determinants of new onset AF in HCM patients. Results Compared to control subjects, HCM patients had higher LA antero-posterior diameter, lower LA ejection fraction and lower LA reservoir (19.9 [17.1, 22.2], 21.6 [19.9, 22.9], P = 0.047) and conduit strain (10.6 ± 4.4, 13.7 ± 3.3, P = 0.002). LA booster strain did not differ between healthy controls and HCM patients, but HCM patients who developed new onset AF (n = 33) had lower booster strain (7.6 ± 3.3, 9.5 ± 3.0, P = 0.001) than those that did not (n = 205). In separate multivariate models, age, LA ejection fraction, and LA booster and reservoir strain were each independent determinants of AF. Age ≥ 55 years was the strongest determinant (HR 6.62, 95% CI 2.79–15.70), followed by LA booster strain ≤ 8% (HR 3.69, 95% CI 1.81–7.52) and LA reservoir strain ≤ 18% (HR 2.56, 95% CI 1.24–5.27). Conventional markers of HCM phenotypic severity, age and sudden death risk factors were associated with LA strain components. Conclusions LA strain components are impaired in HCM and, together with age, independently predicted the risk of new onset AF. Increasing age and phenotypic severity were associated with LA strain abnormalities. Our findings suggest that the routine assessment of LA strain components and consideration of age could augment LA size in predicting risk of AF, and potentially guide prophylactic anticoagulation use in HCM.

Introduction: Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes that alter myocardial contractility and relaxation. Three-dimensional myocardial deformation analysis (3D-MDA) may elucidate left ventricular (LV) abnormalities associated with sarcomere genotype status. Hypothesis: We hypothesize that HCM patients with sarcomere mutations have changes in myocardial contractility profiles that are associated with adverse LV architectural changes. Methods: 3D-MDA was measured using validated feature-tracking software applied to 2D cine cardiac MRI studies in 2,221 genotyped patients within the NHLBI HCM Registry. Results: Baseline, cardiac MRI, and 3D MDA-derived strain characteristics stratified by sarcomere status are shown in Table 1. Sarcomere positive patients were younger, had less LV outflow tract obstruction and lower indexed LV mass, but similar LVEF and trend towards higher serum NT-proBNP levels. Maximal wall thickness, measures of diffuse myocardial fibrosis (native T1, extracellular volume fraction) were elevated with corresponding reduction in global radial strain. Global minimum principal and epicardial layer conventional strain values were higher in sarcomere positive patients. Epicardial minimum principal strain was highly correlated with indexed LV mass (r=0.42, P Conclusions: Sarcomere positive HCM patients had differences in myocardial deformation strain profiles that were correlated to LV architectural changes and NT-proBNP levels despite lower indexed LV mass. More sensitive measures of contractile dysfunction may help elucidate pathophysiological mechanisms by which sarcomere mutations cause disease progression and adverse clinical outcomes in HCM.

Objective The purpose of this study was to determine the feasibility of image-guided laser ablation of demineralization from tooth occlusal surfaces using coaxial near-infrared (NIR) and CO2 lasers. Materials and methods A CO2 laser operating at a wavelength of 9.3-μm was combined with a thulium-doped fiber laser operating at 1880-nm for the selective removal of simulated occlusal caries lesions from 10 tooth samples. Serial NIR reflectance images at 1880-nm were used to guide the CO2 laser for image-guided laser ablation. Polarization-sensitive optical coherence tomography (PS-OCT) was used to assess the initial depth of the lesions before removal and assess the volume of sound and demineralized tissue removed by the CO2 laser. Results PS-OCT scans indicated that roughly ∼99% of the lesion was removed by image-guided laser ablation. A mean volume of 0.191-mm3 or 11.9-μm/voxel of excess enamel was removed during lesion removal. Conclusion A co-aligned NIR/CO2 laser scanning system has great potential for the highly selective removal of dental decay (demineralization). Lasers Surg. Med. 51:176-184, 2019. © 2018 Wiley Periodicals, Inc.

Objective The purpose of this study is to assemble a laser system for the selective removal of dental composite from tooth surfaces, that is feasible for clinical use incorporating a spectral feedback system, a scanning system, articulating arm and a clinical hand-piece, and evaluate the performance of that system on extracted teeth. Methods Ten extracted teeth were collected and small fillings were placed on the occlusal surface of each tooth. A clinical system featuring a CO2 laser operating at 50 Hz and spectral optical feedback was used to remove the composite. Removal was confirmed using a cross polarized optical coherence tomography (CP-OCT) system designed for clinical use. Results The system was capable of rapidly removing composite from small preparations on tooth occlusal surfaces with a mean loss of enamel of less than 20 μm. Conclusion We have demonstrated that spectral feedback can be successfully employed in an automated system for composite removal by incorporating dual photodiodes and a galvanometer controlled CO2 laser. Additionally, the use of registered OCT images presents as a viable method for volumetric benchmarking. Overall, this study represents the first implementation of spectral feedback into a clinical hand-piece and serves as a benchmark for a future clinical study. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.

INTRODUCTION Radiographic methods have poor sensitivity for occlusal lesions and by the time the lesions are radiolucent they have typically progressed deep into the dentin. New more sensitive imaging methods are needed to detect occlusal lesions. In this study, cross-polarization optical coherence tomography (CP-OCT) and near-IR imaging were used to image questionable occlusal lesions (QOC's) that were not visible on radiographs but had been scheduled for restoration on 30 test subjects. METHODS Near-IR reflectance and transillumination probes incorporating a high definition InGaAs camera and near-IR broadband light sources were used to acquire images of the lesions before restoration. The reflectance probe utilized cross-polarization and operated at wavelengths from 1,500 to 1,700 nm where there is an increase in water absorption for higher contrast. The transillumination probe was operated at 1,300 nm where the transparency of enamel is highest. Tomographic images (6 × 6 × 7 mm3 ) of the lesions were acquired using a high-speed swept-source CP-OCT system operating at 1,300 nm before and after removal of the suspected lesion. RESULTS Near-IR reflectance imaging at 1,500-1,700 nm yielded significantly higher contrast (P

Objective: This study aims to compare the incidence of ventilation/perfusion (V/Q) scans interpreted as indeterminate for the diagnosis of pulmonary embolism (PE) using single-photon emission computed tomography (SPECT) versus planar scintigraphy and to consider the effect of variable interpretation of single subsegmental V/Q mismatch (SSM). Methods: A total of 1300 consecutive V/Q scans were retrospectively reviewed. After exclusion and matching for age and sex, 542 SPECT and 589 planar scans were included in the analysis. European Association of Nuclear Medicine guidelines were used to interpret the V/Q scans, initially interpreting SSM as negative scans. Patients with SSM were followed up for 3 months and further imaging for PE was collected. Results: Indeterminate scans were significantly fewer in the SPECT than the planar group on the basis of the initial report (7.7 vs. 12.2%, P

OBJECTIVES: The risk of recurrent venous thromboembolic disease and the management of patients with isolated subsegmental pulmonary embolism (SSPE) remain unclear. We sought to assess the long-term clinical outcome of patients with isolated SSPE demonstrated by isolated subsegmental mismatch found on ventilation/perfusion (V/Q) scans. PATIENTS AND METHODS: We performed a retrospective observational study of 1300 consecutive patients with suspected pulmonary embolism who underwent index V/Q single-photon emission computed tomography between 2012 and 2013. Forty (3%) patients were found to have isolated SSPE identified on V/Q scan. Of the 40 patients with isolated SSPE on V/Q scan, 19 underwent further investigation with computed tomography pulmonary angiogram (CTPA) within 48 h. RESULTS: Among 19 patients who had corroborating CTPA performed concurrently, 94.7% of the SSPEs identified on V/Q were not detectable on CTPA. Of the 40 patients, 10 (25%) were anticoagulated. In a median follow-up of 3.28±0.55 years, all-cause mortality occurred in two patients, recurrence of suspected venous thromboembolism (VTE) occurred in 12 (30%) of 40 patients, but none had confirmed recurrent thromboembolism on further imaging. In the 40 patients with SSPE on V/Q, there was no difference in the risk of recurrence of suspected VTE or mortality between patients treated with anticoagulation and not treated (hazard ratio: 2.04, 95% confidence interval: 0.75-7.28). CONCLUSION: In this case series, a large proportion of patients with isolated SSPE on V/Q imaging were not identified on corroborating CTPA performed within 48 h. In patients with isolated SSPE (identified by isolated subsegmental mismatch on V/Q single-photon emission computed tomography), we found no difference in risk of recurrent suspected VTE or all-cause mortality in those treated with anticoagulation and those not treated.

Myocardial perfusion reserve is impaired in aortic stenosis (AS) even in the absence of epicardial coronary stenosis [(1)][1], which may be due to reduced capillary density and endothelial dysfunction [(2,3)][2]. However, the relationship between histopathological abnormalities of the vasculature

Introduction In aortic stenosis (AS), characterisation of ventricular (LV) remodelling beyond left ventricular mass measurements is lacking. We sought to study the 3-dimensional (3D) geometric LV remodelling pattern in severe AS pre- and post-surgical aortic valve replacement (AVR), and compared it with hypertensive and healthy controls. Methods Ninety-one subjects (36 severe AS, 19 hypertension and 36 healthy controls) underwent cardiac magnetic resonance (CMR). 18 AS patients had a repeat CMR eight-month post-AVR. 3D meshes were reconstructed from the myocardial contours of the CMR cine images. Principle component analysis and linear discrimination analysis were used to derive shape coefficients. Results AS patients had a significant shift in LV axis and apex orientation towards the septum, and more spherical LV shape which were not seen in the hypertensive and healthy control groups. As expected severe AS was associated with thicker and larger LV compared to the other two groups. Post AVR, despite significant reduction in LV thickness and sphericity, interestingly the shift in the LV axis/orientation was unchanged/irreversible (Figure 1). Conclusion Severe AS is characterised by unique remodelling pattern which is not reversible post AVR. The novel shape metrics that comprehensively quantify the LV morphology may be a potential marker for risk stratification in the management of AS. Conflict of Interest none

Myocardial ischemia has long been implicated in promoting arrhythmic events and triggering sudden cardiac death in hypertrophic cardiomyopathy (HCM). However, the evidence for this is scarce due to challenges presented in direct ischemia assessment which generally requires an invasive approach. Blood oxygen level dependent cardiac magnetic resonance (BOLD CMR) permits the non-invasive assessment of tissue oxygenation, without gadolinium contrast, overcoming many limitations suffered by traditional methods. From a clinical perspective, T2-prepared steady-state free precession (T2-SSFP) BOLD is promising, but suffers from reduced diagnostic accuracy, owing to imprecisions in BOLD measurements secondary to heart-rate (HR) dependence. To resolve this, we developed a novel oxygen-sensitive CMR approach, Fast Low Angle Shot (FLASH) interleaved T2-SSFP BOLD, which was designed to eliminate both HR dependence and spatial variations seen with standard T2-SSFP BOLD. A comparison of both standard and novel approaches in 20 healthy subjects confirmed that FLASH-normalised T2-SSFP BOLD is highly reproducible, HR independent and more precise than standard T2-SSFP BOLD. In addition, the mean BOLD effect did not differ between the two methods. Importantly, using this novel approach, one could visualise changes in oxygen-sensitive signal from rest to stress qualitatively, making it feasible for direct incorporation into a clinical work flow. We then set out to test the hypothesis that stress oxygenation (as assessed on FLASH normalised T2-SSFP BOLD) is more powerful that myocardial perfusion reserve (MPRI) at determining arrhythmic risk in HCM patients. Adenosine stress BOLD, first pass perfusion imaging and late gadolinium enhancement CMR were undertaken in 103 genotyped-HCM patients. All patients underwent 24-hour Holter to monitor for evidence of ventricular tachycardia (≥3 beats, ≥120 beats per minute). Thirty-two age- and sex-matched healthy subjects served as controls. Although both stress oxygenation and MPRI were impaired in HCM, only stress oxygenation, but not MPRI, associated with ventricular tachycardia on univariate analysis. There was a step-wise increase in ventricular tachycardia prevalence with decreasing quartiles of stress oxygenation. HCM patients with the lowest quartile of oxygenation were at a three-fold increased risk of ventricular tachycardia (OR 3.04, p=0.04) after adjusting for LGE mass, age and baseline risk of sudden cardiac death. Sarcomeric mutation status was an independent determinant of stress oxygenation, irrespective of the extent of hypertrophy, MPRI or LGE burden (univariate predictors). In conclusion, we have successfully developed and implemented a novel oxygen-sensitive CMR method which has provided important insights into the role of stress oxygenation as a promising biomarker of arrythmic risk and potential therapeutic target for drug discovery in HCM.

Background Impaired myocardial perfusion reserve occurs in pressure overload hypertrophy such as in severe aortic stenosis (AS) despite unobstructed epicardial coronaries. However the pathological mechanisms underlying this are poorly understood. We sought to assess myocardial perfusion reserve in severe AS by stress perfusion cardiovascular magnetic resonance (CMR), and examine the findings in relation to the histological evidence of vascular changes in the myocardium. Methods Fourteen patients with severe AS and unobstructed epicardial coronaries underwent adenosine stress perfusion CMR before and 6 months after surgical aortic valve replacement (AVR). Myocardial biopsies were obtained during AVR and stained using CD31 +for endothelium, smooth muscle actin (SMA) for smooth muscle, and picrosirius red for fibrosis. Nine age- and sex- matched post-mortem myocardial samples served as histological controls. Results When compared to controls, the myocardium of patients with severe AS had reduced vessel density, total quantity of SMA +ve and CD31 +ve, in addition to the expected increase in fibrosis. There was absence of CD31 +ve endothelium in SMA +ve arterioles, indicating endothelial loss. (Figure 1) Importantly, patients with an aortic valve area (AVA) ≤0.8cm2 had greater endothelial loss compared to those with an AVA >0.8 and≤1.0cm2 (1.34%±0.44% vs 2.84±1.03%, p=0.006), and endothelial loss also correlated with myocardial perfusion reserve index (MPRI), r=0.66, p=0.019. MPRI improved significantly post AVR (from 0.95±0.17 to 1.50±0.43, p=0.018). Conclusion In severe AS, there is microvascular rarefaction and loss of endothelium, which is more pronounced in patients with the most severe aortic valve narrowing. This appears to be an underlying mechanism for reduced myocardial perfusion reserve, which may be reversible post AVR.

Background Myocardial ischaemia is believed to promote fatal life-threatening ventricular arrhythmias in hypertrophic cardiomyopathy (HCM). Oxygen sensitive cardiac magnetic resonance (CMR) or blood oxygen level dependent (BOLD) imaging can detect blunted myocardial oxygenation during vasodilator stress in HCM. Whether or not impairment in stress oxygenation is associated with ventricular arrythmia risk is unknown. Objectives To investigate the relationship between blunted stress oxygenation and ventricular arrhythmia in HCM and examine the determinants of stress oxygenation in HCM. Methods 103 genotyped HCM patients and 32 (age, gender and body mass index matched) healthy controls underwent adenosine stress BOLD, stress first pass perfusion imaging and late gadolinium imaging (LGE) to assess stress oxygenation, myocardial perfusion reserve index (MPRI), and fibrosis burden respectively. Stress oxygenation response (BOLD ΔSI) was estimated as a relative increase in oxygen sensitive BOLD signal intensity from rest to peak vasodilator stress. All HCM patients had 24-holter monitoring to assess for ventricular tachycardia (≥3 beats,≥120 beats per minute). Results As expected, both MPRI (1.5±0.4 v 2.0±0.3, p Conclusion In HCM, impaired stress-induced oxygenation is associated with an increased risk of ventricular arrhythmia and may represent a novel biomarker of arrhythmic risk. Sarcomeric mutation status independently predicts a blunted stress oxygenation response in HCM.

Background The current assessment of hypertrophic cardiomyopathy (HCM) places emphasis on left ventricular (LV) function which is usually preserved in early disease. There are limited data on right ventricular (RV) assessment in HCM, progressive functional changes, and impact of RV dysfunction on clinical outcomes. Objectives To examine the natural history of RV functional changes (ejection fraction and strain) and investigate its prognostic role in HCM. Methods 311 patients (mean age 52±15 years) with HCM and preserved LV function (ejection fraction; EF ≥50%) underwent cardiac magnetic resonance (CMR) imaging and were compared to age- and sex- matched healthy controls (n=30). In 71 patients, follow-up CMR imaging was further undertaken at a median interval of 5.3 years. All patients were followed up for a composite endpoint of adverse cardiovascular outcomes, including new-onset atrial fibrillation, ventricular arrhythmia, hospitalisation due to heart failure or embolic events, or cardiovascular death. Results HCM patients exhibited lower RV ejection fraction (RVEF) and global peak systolic strains (radial/circumferential/longitudinal) on feature-tracking analysis of cine images than healthy controls. On follow up CMR imaging, RVEF, peak RV circumferential and longitudinal strains decreased over time while LVEF remained preserved. All patients were followed up clinically for a median duration of 4.4 years. Both reduced RVEF and RV longitudinal strain were independent predictors of ventricular arrhythmias and composite cardiovascular endpoint (arrhythmia, cardiac hospitalisation and cardiovascular death), after adjusting for baseline NYHA class, medication use, maximal LV wall thickness, and late gadolinium enhancement. Patients with RVEF −16.3%) demonstrated a higher risk of ventricular arrhythmias (HR 2.20, 95% CI 1.20 to 4.01, figure 1C) and composite cardiac events (HR 2.49, 95% CI 1.61 to 3.84, figure 1D) compared to others. Conclusions Despite preserved LVEF, RVEF and strain decline over time in HCM. RVEF and strain predict the occurrence of adverse cardiovascular outcomes and may have a role in prognostic risk stratification in HCM.

Near Infrared Reflectance (NIR) is a new imaging technology that detects dental caries (decay) on tooth occlusal surfaces and in the interproximal contact sites between teeth. Conventional techniques, mostly dental x-rays, do not provide the high sensitivity and specificity at the vulnerable pits and fissure regions. The contrast of demineralization on tooth surfaces changes with increasing severity and the magnitude of that change with depth depends on the wavelength. The purpose of this study is to determine how the contrast changes with depth as a function of wavelength. Demineralization of varying depth was produced in 1.5 × 1.5 mm exposed windows after 1, 2, 3, 4, and 5 days of exposure to a demineralizing solution at pH 4.5. Lesions were imaged at 405, 630, 850, 1300, 1460, 1535, 1675, and 1950-nm with multiple imaging systems. The highest lesion contrast was measured at 1950-nm.

It is challenging to identify demineralized areas of root lesions due to cervical erosion, calculus formation, and heavy staining of dentin. We have found that root caries can be imaged with extremely high contrast at short wavelength IR (SWIR) wavelengths beyond 1500-nm. Lasers are well suited for the selective removal of caries lesions from tooth surfaces. A CO(2) laser operating at a wavelength of 9.3-μm was combined with a thulium-doped fiber laser operating at 1880-nm for the selective removal of root caries lesions from extracted teeth. Serial SWIR reflectance images at 1880-nm were used to guide the CO(2) laser for image-guided laser ablation. Cross polarization optical coherence tomography (CP-OCT) was used to assess the initial depth of the lesions before removal and assess the volume of sound and demineralized tissue removed by the CO(2) laser. With this image-guided approach, we believe we can achieve highly selective lesion removal and minimal damage to surrounding sound tissues.

Introduction Several studies suggest that near-IR imaging methods at wavelengths longer than 1,300 nm have great potential for caries detection. In this study, the diagnostic performance of both near-IR transillumination and near-IR reflectance was assessed on teeth scheduled for extraction due to orthodontic treatment (n = 109 teeth on 40 test subjects). Methods Three intra-oral near-IR imaging probes were fabricated for the acquisition of in vivo images using a high definition InGaAs camera and near-IR broadband light sources. Two transillumination probes provided occlusal and approximal images using 1,300 nm light which manifests the highest transparency in enamel. A third reflectance probe utilized cross-polarization and operated at wavelengths greater than 1,500 nm where water absorption is higher which reduces the reflectivity of sound tissues, significantly increasing lesion contrast. Teeth were collected after extraction and sectioned and examined with polarized light microscopy and microradiography which served as the gold standard. In addition, radiographs were taken of the teeth and the diagnostic performance of near-IR imaging was compared with radiography. Results Near-IR imaging was significantly more sensitive (P

Introduction Studies have shown that cross-polarization optical coherence tomography (CP-OCT) can be used to image the internal structure of carious lesions in vivo. The objective of this study was to show that CP-OCT can be used to monitor changes in the internal structure of early active carious lesions on smooth surfaces during non-surgical intervention with fluoride. Methods Lesions on the smooth surfaces of teeth were imaged using CP-OCT on 17 test subjects. Lesion structural changes were monitored during fluoride varnish application at 6-week intervals for 30 weeks. The lesion depth (Ld), integrated reflectivity (ΔR), and surface zone thickness (Sz) were monitored. Results A distinct transparent surface zone that may be indicative of lesion arrestment was visible in CP-OCT images on 62/63 lesions before application of fluoride varnish. The lesion depth and internal structure were resolved for all the lesions. The overall change in the mean values for Ld, ΔR, and Sz for all the lesions was minimal and was not significant during the study (P > 0.05). Only 5/63 lesions manifested a significant increase in Sz during intervention. Conclusion Even though it appears that most of the lesions manifested little change with fluoride varnish application in the 30 weeks of the study, CP-OCT was able to measure the depth and internal structure of all the lesions including the thickness of the important transparent surface zone located at the surface of the lesions, indicating that CP-OCT is ideally suited for monitoring lesion severity in vivo. Lasers Surg. Med. © 2016 Wiley Periodicals, Inc.

Introduction Studies have shown that reflectance images at near-IR wavelengths coincident with higher water absorption are well-suited for image-guided laser ablation of carious lesions since the contrast between sound and demineralized enamel is extremely high and interference from stains is minimized. The objective of this study was to demonstrate that near-IR reflectance images taken at a wavelength range of 1,500–1,700 nm can be used to guide a 9.3 μm CO2 laser for the selective ablation of early demineralization on tooth occlusal surfaces.

Resistant hypertension (RHTN) is defined as uncontrolled office blood pressure (>140/90 mmHg) despite treatment with maximum tolerated doses of three or more antihypertensive agents from at least three different classes, including a diuretic. The prevalence of RHTN is about 8–18% in hypertensive patients and confers greatly increased risk of cardiovascular morbidity and mortality.

Previous studies have shown that reflectance imaging at wavelengths greater than 1200-nm can be used to image demineralization on tooth occlusal surfaces with high contrast and without the interference of stains. In addition, these near-IR imaging systems can be integrated with laser ablation systems for the selective removal of carious lesions. Higher wavelengths, such as 1950-nm, yield higher lesion contrast due to higher water absorption and lower scattering. In this study, a point-to-point scanning system employing diode and fiber lasers operating at 1450, 1860, 1880, and 1950-nm was used to acquire reflected light images of the tooth surface. Artificial lesions were imaged at these wavelengths to determine the highest lesion contrast. Near-IR images at 1880-nm were used to demarcate lesion areas for subsequent selective carious lesion removal using a new compact air-cooled CO2 laser prototype operating at 9.3-µm. The highest lesion contrast was at 1950-nm and the dual NIR/CO2 laser system selectively removed the simulated lesions with a mean loss of only 12-µm of sound enamel.

Recent studies have shown that near-IR (NIR) imaging methods such as NIR reflectance can be used to image lesions on proximal surfaces, and optical coherence tomography (OCT) can be used to measure the depth of those lesions below the tooth surface. These imaging modalities can be used to acquire high contrast images of demineralized tooth surfaces, and 2-D and 3-D images can be extracted from this data. At NIR wavelengths longer than 1200-nm, there is no interference from stains and the contrast is only due to the increased light scattering of the demineralization. Previous studies have shown that image-guided laser ablation can be used to remove occlusal lesions, but its use for the removal of subsurface lesions on proximal surfaces has not been investigated. The objective of this study is to demonstrate that simultaneously scanned NIR and CO2 lasers can be used to selectively remove natural and artificial interproximal caries lesions with minimal damage to sound tooth structure. In this study, images of simulated and natural interproximal lesions on extracted teeth were imaged using a digital microscope, a scanned 1460-nm superluminescent laser diode with an InGaAs detector and a cross polarization OCT system operating at 1300-nm. The lesions were subsequently removed with a CO2 laser operating at 9.3-µm and the dental handpiece and the volume of sound tissue removed was compared.

Recent studies have shown that near-IR (NIR) imaging methods such as NIR reflectance can be used to image lesions on proximal surfaces, and optical coherence tomography (OCT) can be used to measure the depth of those lesions below the tooth surface. These imaging modalities can be used to acquire high contrast images of demineralized tooth surfaces, and 2-D and 3-D images can be extracted from this data. At NIR wavelengths longer than 1200-nm, there is no interference from stains and the contrast is only due to the increased light scattering of the demineralization. Previous studies have shown that image-guided laser ablation can be used to remove occlusal lesions, but its use for the removal of subsurface lesions on proximal surfaces has not been investigated. The objective of this study is to demonstrate that simultaneously scanned NIR and CO2 lasers can be used to selectively remove natural and artificial interproximal caries lesions with minimal damage to sound tooth structure. In this study, images of simulated and natural interproximal lesions on extracted teeth were imaged using a digital microscope, a scanned 1460-nm superluminescent laser diode with an InGaAs detector and a cross polarization OCT system operating at 1300-nm. The lesions were subsequently removed with a CO2 laser operating at 9.3-µm and the dental handpiece and the volume of sound tissue removed was compared.

Previous studies have shown that reflectance imaging at wavelengths greater than 1200-nm can be used to image demineralization on tooth occlusal surfaces with high contrast and without the interference of stains. In addition, these near-IR imaging systems can be integrated with laser ablation systems for the selective removal of carious lesions. Higher wavelengths, such as 1950-nm, yield higher lesion contrast due to higher water absorption and lower scattering. In this study, a point-to-point scanning system employing diode and fiber lasers operating at 1450, 1860, 1880, and 1950-nm was used to acquire reflected light images of the tooth surface. Artificial lesions were imaged at these wavelengths to determine the highest lesion contrast. Near-IR images at 1880-nm were used to demarcate lesion areas for subsequent selective carious lesion removal using a new compact air-cooled CO2 laser prototype operating at 9.3-μm. The highest lesion contrast was at 1950-nm and the dual NIR/CO2 laser system selectively removed the simulated lesions with a mean loss of only 12-μm of sound enamel.

Previous studies have established that carious lesions can be imaged with high contrast using near-IR wavelengths coincident with high water absorption, namely 1450-nm, without the interference of stains. It has been demonstrated that computer-controlled laser scanning systems utilizing IR lasers operating at high pulse repetition rates can be used for serial imaging and selective removal of caries lesions. In this study, a point-to-point scanning system was developed integrating a 1450-nm diode laser with the CO2 ablation laser. This approach is advantageous since it does not require an expensive near-IR camera. In this pilot study, we demonstrate the feasibility of a combined NIR and IR laser system for the selective removal of carious lesions.

ObjectiveThe purpose of this study is to assemble a laser system for the selective removal of dental composite from tooth surfaces, that is feasible for clinical use incorporating a spectral feedback system, a scanning system, articulating arm and a clinical hand-piece, and evaluate the performance of that system on extracted teeth.MethodsTen extracted teeth were collected and small fillings were placed on the occlusal surface of each tooth. A clinical system featuring a CO2 laser operating at 50 Hz and spectral optical feedback was used to remove the composite. Removal was confirmed using a cross polarized optical coherence tomography (CP-OCT) system designed for clinical use.ResultsThe system was capable of rapidly removing composite from small preparations on tooth occlusal surfaces with a mean loss of enamel of less than 20 μm.ConclusionWe have demonstrated that spectral feedback can be successfully employed in an automated system for composite removal by incorporating dual photodiodes and a galvanometer controlled CO2 laser. Additionally, the use of registered OCT images presents as a viable method for volumetric benchmarking. Overall, this study represents the first implementation of spectral feedback into a clinical hand-piece and serves as a benchmark for a future clinical study. Lasers Surg. Med. 49:658-665, 2017. © 2017 Wiley Periodicals, Inc.

Both laser irradiation and fluoride treatment alone are known to provide increased resistance to acid dissolution. CO2 lasers tuned to a wavelength of 9.3 μm can be used to efficiently convert the carbonated hydroxyapatite of enamel to a much more acid resistant purer phase hydroxyapatite (HAP). Further studies have shown that fluoride application to HAP yields fluoroapatite (FAP) which is even more resistant against acid dissolution. Previous studies show that CO2 lasers and fluoride treatments interact synergistically to provide significantly higher protection than either method alone, but the mechanism of interaction has not been elucidated. We recently observed the formation of microcracks or a “crazed” zone in the irradiated region that is resistant to demineralization using high-resolution microscopy. The microcracks are formed due to the slight contraction of enamel due to transformation of carbonated hydroxyapatite to the more acid resistant pure phase hydroxyapatite (HAP) that has a smaller lattice. In this study, we test the hypothesis that these small cracks will provide greater adhesion for topical fluoride for greater protection against acid demineralization.

UV and IR lasers can be used to specifically target protein, water, and the mineral phase of dental hard tissues to produce varying changes in surface morphology. In this study, we irradiated enamel and dentin surfaces with various combinations of lasers operating at 0.355, 2.94, and 9.4 μm, exposed those surfaces to topical fluoride, and subsequently evaluated the influence of these changes on surface morphology and permeability. Digital microscopy and surface dehydration rate measurements were used to monitor changes in the samples overtime. The surface morphology and permeability (dehydration rate) varied markedly with the different laser treatments on enamel. On dentin, fluoride was most effective in reducing the permeability.

Radiographic methods have poor sensitivity for occlusal lesions and by the time the lesions are radiolucent they have typically progressed deep into the dentin. New more sensitive imaging methods are needed to detect occlusal lesions. In this study, cross-polarization optical coherence tomography (CP-OCT) and near-IR imaging were used to image questionable occlusal lesions (QOC's) that were not visible on radiographs but had been scheduled for restoration on 30 test subjects.Near-IR reflectance and transillumination probes incorporating a high definition InGaAs camera and near-IR broadband light sources were used to acquire images of the lesions before restoration. The reflectance probe utilized cross-polarization and operated at wavelengths from 1,500 to 1,700 nm where there is an increase in water absorption for higher contrast. The transillumination probe was operated at 1,300 nm where the transparency of enamel is highest. Tomographic images (6 × 6 × 7 mmNear-IR reflectance imaging at 1,500-1,700 nm yielded significantly higher contrast (P 0.05) of the demineralization in the occlusal grooves compared with visible reflectance imaging. Stains in the occlusal grooves greatly reduced the lesion contrast in the visible range yielding negative values. Only half of the 26 lesions analyzed showed the characteristic surface demineralization and increased reflectivity below the dentinal-enamel junction (DEJ) in 3D OCT images indicative of penetration of the lesion into the dentin.This study demonstrates that near-IR imaging methods have great potential for improving the early diagnosis of occlusal lesions. Lasers Surg. Med. 49:215-224, 2017. © 2017 Wiley Periodicals, Inc.

Previous studies have demonstrated that the permeability changes due to the surface modification of dentin can be quantified via thermal imaging during dehydration. The CO2 laser has been shown to remove the smear layer and disinfect root canals. Moreover, thermal modification via CO2 laser irradiation can be used to convert dentin into a highly mineralized enamel-like mineral. The purpose of this study is to evaluate the radicular dentin surface modification after CO2 laser irradiation by measuring the permeability with thermal imaging. Human molar specimens (n=12) were sectioned into 4 axial walls of the pulp chamber and treated with either 10% NaClO for 1 minute, 5% EDTA for 1 minute, CO2 laser or none. The CO2 laser was operated at 9.4 μm with a pulse duration of 26 μs, pulse repetition rate of 300 Hz and a fluence of 13 J/cm2. The samples were dehydrated using an air spray for 60 seconds and imaged using a thermal camera. The resulting surface morphological changes were assessed using 3D digital microscopy. The images from digital microscopy confirmed melting of the mineral phase of dentin. The area enclosed by the time-temperature curve during dehydration, ΔQ, measured with thermal imaging increased significantly with treatments with EDTA and the CO2 laser (P

Selective removal of caries lesions with high precision is best accomplished using lasers operating at high pulse repetition rates utilizing small spot sizes. Conventional flash-lamp pumped Er:YAG lasers are poorly suited for this purpose, but new diode-pumped solid-state (DPSS) Er:YAG lasers have become available operating at high pulse repetition rates. Microradiography was used to determine the mineral content of the demineralized dentin of 200-μm thick sections with natural caries lesions prior to laser ablation. The purpose of this study was to explore the use of a DPSS Er:YAG laser for the selective removal of demineralized dentin and natural occlusal lesions on extracted teeth.

Introduction Since optical coherence tomography (OCT) is well suited for measuring small dimensional changes on tooth surfaces, OCT has great potential for monitoring tooth erosion. Previous studies have shown that enamel areas ablated by a carbon dioxide laser manifested lower rates of erosion compared to the non-ablated areas. The purpose of this study was to develop a model to monitor erosion in vitro that could potentially be used in vivo. Methods Thirteen bovine enamel blocks were used in this in vitro study. Each 10 mm × 2 mm block was partitioned into five regions, the central region was unprotected, the adjacent windows were irradiated by a CO2 laser operating at 9.3 µm with a fluence of 2.4 J/cm2, and the outermost windows were coated with acid resistant varnish. The samples were exposed to a pH cycling regimen that caused both erosion and subsurface demineralization for 2, 4 and 6 days. The surfaces were scanned using a time-domain polarization sensitive optical coherence tomography (PS-OCT) system and the degree of surface loss (erosion) and the integrated reflectivity with lesion depth was calculated for each window. Results There was a large and significant reduction in the depth of surface loss (erosion) and the severity of demineralization in the areas irradiated by the laser. Conclusion Irradiation of the enamel surface with a pulsed carbon dioxide laser at sub-ablative intensities results in significant inhibition of erosion and demineralization under the acid challenge employed in this study. In addition, these results suggest that it may be feasible to modify regions of the enamel surface using the laser to serve as reference marks to monitor the rate of erosion in vivo. Lasers Surg. Med. 46:672–678, 2014. © 2014 Wiley Periodicals, Inc.

ObjectivesThe aim of this study was to test the hypothesis that cross-polarization optical coherence tomography (CP-OCT) can be used to longitudinally monitor demineralization peripheral to orthodontic brackets in an extended clinical study.MethodsA high-speed CP-OCT system was used to acquire 3D volumetric images of the area at the base of orthodontic brackets over a period of 12 months after placement. The reflectivity was measured at 3-month intervals for 12 months to determine if there was increased demineralization. Two teeth were monitored on 20 test subjects and the brackets were bonded using two types of adhesives. This was a randomized controlled clinical study with a split mouth design such that each subject served as his or her own control. On one side, the control premolar was bonded with a bonding agent (Adper Scotchbond from 3M ESPE, St. Paul, MN) and composite (Transbond XT from 3M Unitek, Monrovia, CA) that lacked fluoride. On the other side, the experimental premolar was bonded with a fluoride releasing glass ionomer cement (GC Fuji Ortho LC from GC America, Alsip, IL).ResultsThere was a small but significant increase in the calculated lesion depth and integrated reflectivity over that depth (ΔR) for both adhesive types (p

We report a case of late presentation of metastatic renal cell carcinoma (RCC) demonstrating intense 111In-DTPA-octreotide uptake in pancreas without recurrence at the primary site. Immunohistochemistry study revealed somatostatin receptor subtype 2 of metastatic RCC preferentially expressed on tumor endothelial cells. The typical hypervascular features of RCC with intense homogeneous contrast enhancement in the arterial phase on CT should raise the possibility of metastatic RCC. This case illustrates that RCC can demonstrate high octreotide uptake in abdominal metastases.

Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a 10- to 20-fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4 mm × 4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hours exposure to a demineralizing solution at pH 4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths >500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two-dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion contrast in the visible does not accurately reflect the large variation in the lesion severity. Reflectance measurements at certain near-IR wavelengths more accurately reflect variation in the depth and severity of the lesions. Conclusion The results of the study suggest that near-IR reflectance measurements at longer wavelengths coincident with higher water absorption are better suited for imaging early caries lesions. Lasers Surg. Med. 46:203–215, 2014. © 2014 Wiley Periodicals, Inc.

Several studies have demonstrated the potential of cross-polarization optical coherence tomography (CP-OCT) to quantify the severity of early caries lesions (tooth decay) on tooth surfaces. The purpose of this study is to show that 2D images of the lesion depth and the integrated reflectivity can be used to accurately represent the severity of early lesions. Simulated early lesions of varying severity were produced on tooth samples using simulated lesion models. Methods were developed to convert the 3D CP-OCT images of the samples to 2D images of the lesion depth and lesion integrated reflectivity. Calculated lesion depths from OCT were compared with lesion depths measured from histological sections examined using polarized light microscopy. The 2D images of the lesion depth and integrated reflectivity are well suited for visualization of early demineralization.

Background With substantial public interest in complementary and alternative medicine (CAM), future doctors will need to provide evidence-based advice on their safety and efficacy. Informing medical students of CAM therefore becomes increasingly important. Objective To determine the extent and context of teaching on evidence-based medicine (EBM) and CAM in UK medical schools from the student perspective. Methods A web-based, 10-item anonymous questionnaire was sent to selected UK medical students to assess their experience of teaching on EBM (including statistics) and CAM. The questionnaire measured the following parameters: number of lectures on EBM, number of lectures or workshops on statistics, number of lectures or availability of student-selected components on CAM, rating of CAM teaching as critical, uncritical or discursive, and quality of feedback after placements with CAM practitioners. Results There were 95 student responses representing 25 different medical courses. Of the respondents, 54% had received lectures on CAM in the core course. Of these students, 46% stated the lectures were ‘critical’, 16% ‘uncritical’ and 39% ‘discursive’. Of the 33 who reported on placements with CAM practitioners, 61% stated there was no feedback, 12% received feedback from a specialist tutor, 15% from a non-specialist facilitator, 9% via peer-led reflection and 3% through a tutor-marked written account. Conclusions Teaching of EBM, statistics and CAM is covered by most UK medical schools. However, we have identified areas in which CAM teaching could be improved. The survey demonstrates a need for UK curriculum coordinators to review the teaching of CAM-related components in their courses.

Introduction In vivo and in vitro studies have shown that high contrast images of tooth demineralization can be acquired in the near-infrared (near-IR) without the interference of stain. The purpose of this study is to compare the lesion contrast in reflectance at near-IR wavelengths coincident with high water absorption with those in the visible, the near-IR at 1,300 nm and with fluorescence measurements for early lesions in occlusal surfaces. Methods Twenty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4 × 4 mm window in the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the exposed windows after 1- and 2-day exposure to a demineralizing solution at pH 4.5. Lesions were imaged using near-IR reflectance at three wavelengths, 1,300, 1,460, and 1,600 nm using a high definition InGaAs camera. Visible light reflectance, and fluorescence with 405 nm excitation and detection at wavelengths greater than 500 nm were also used to acquire images for comparison. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Results The contrast of both the 1- and 2-day lesions were significantly higher (P