A crystallin mutant cataract with mineral deposits.

Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we characterized the lenses from a nonconnexin mutant mouse cataract model. By cosegregation of the phenotype with a satellite marker and genomic sequencing, we identified the mutant as a 5-bp duplication in the γC-crystallin gene (Crygcdup). Homozygous mice developed severe cataracts early, and heterozygous animals developed small cataracts later in life. Immunoblotting studies showed that the mutant lenses contained decreased levels of crystallins, connexin46, and connexin50 but increased levels of resident proteins of the nucleus, endoplasmic reticulum, and mitochondria. The reductions in fiber cell connexins were associated with a scarcity of gap junction punctae as detected by immunofluorescence and significant reductions in gap junction-mediated coupling between fiber cells in Crygcdup lenses. Particles that stained with the calcium deposit dye, Alizarin red, were abundant in the insoluble fraction from homozygous lenses but nearly absent in wild-type and heterozygous lens preparations. Whole-mount homozygous lenses were stained with Alizarin red in the cataract region. Mineralized material with a regional distribution similar to the cataract was detected in homozygous lenses (but not wild-type lenses) by micro-computed tomography. Attenuated total internal reflection Fourier-transform infrared microspectroscopy identified the mineral as apatite. These results are consistent with previous findings that loss of lens fiber cell gap junctional coupling leads to the formation of calcium precipitates. They also support the hypothesis that pathologic mineralization contributes to the formation of cataracts of different etiologies.

Stable patients with suspected myocardial ischemia: comparison of machine-learning computed tomography-based fractional flow reserve and stress perfusion cardiovascular magnetic resonance imaging to detect myocardial ischemia.

BACKGROUND: Machine-Learning Computed Tomography-Based Fractional Flow Reserve (CT-FFRML) is a novel tool for the assessment of hemodynamic relevance of coronary artery stenoses. We examined the diagnostic performance of CT-FFRML compared to stress perfusion cardiovascular magnetic resonance (CMR) and tested if there is an additional value of CT-FFRML over coronary computed tomography angiography (cCTA). METHODS: Our retrospective analysis included 269 vessels in 141 patients (mean age 67 ± 9 years, 78% males) who underwent clinically indicated cCTA and subsequent stress perfusion CMR within a period of 2 months. CT-FFRML values were calculated from standard cCTA. RESULTS: CT-FFRML revealed no hemodynamic significance in 79% of the patients having ≥ 50% stenosis in cCTA. Chi2 values for the statistical relationship between CT-FFRML and stress perfusion CMR was significant (p < 0.0001). CT-FFRML and cCTA (≥ 70% stenosis) provided a per patient sensitivity of 88% (95%CI 64-99%) and 59% (95%CI 33-82%); specificity of 90% (95%CI 84-95%) and 85% (95%CI 78-91%); positive predictive value of 56% (95%CI 42-69%) and 36% (95%CI 24-50%); negative predictive value of 98% (95%CI 94-100%) and 94% (95%CI 90-96%); accuracy of 90% (95%CI 84-94%) and 82% (95%CI 75-88%) when compared to stress perfusion CMR. The accuracy of cCTA (≥ 50% stenosis) was 19% (95%CI 13-27%). The AUCs were 0.89 for CT-FFRML and 0.74 for cCTA (≥ 70% stenosis) and therefore significantly different (p < 0.05). CONCLUSION: CT-FFRML compared to stress perfusion CMR as the reference standard shows high diagnostic power in the identification of patients with hemodynamically significant coronary artery stenosis. This could support the role of cCTA as gatekeeper for further downstream testing and may reduce the number of patients undergoing unnecessary invasive workup.

Structure-Property Effects in the Generation of Transient Aqueous Benzoic Acid Anhydrides by Carbodiimide Fuels.

The design of dissipative systems, which operate out-of-equilibrium by consuming chemical fuels, is challenging. As yet, there are a few examples of privileged fuel chemistries that can be broadly applied in abiotic systems in the same way that ATP hydrolysis is exploited throughout biochemistry. The key issue is that designing nonequilibrium systems is inherently about balancing the relative rates of coupled reactions. The use of carbodiimides as fuels to generate transient aqueous carboxylic anhydrides has recently been used in examples of new nonequilibrium materials and supramolecular assemblies. Here, we explore the kinetics of formation and decomposition of a series of benzoic anhydrides generated from the corresponding acids and EDC under typical conditions (EDC = N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride). The reactions can be described by a simple mechanism that merges known behavior for the two processes independently. Structure-property effects in these systems are dominated by differences in the anhydride decomposition rate. The kinetic parameters allow trends in concentration-dependent properties to be simulated, such as reaction lifetimes, peak anhydride concentrations, and yields. For key properties, there are diminishing returns with the addition of increasing amounts of fuel. These results should provide useful guidelines for the design of functional systems making use of this chemistry.

Analysis of Counterfeit Coated Tablets and Multi-Layer Packaging Materials Using Infrared Microspectroscopic Imaging.

An effective method for detecting and characterizing counterfeit finished dosage forms and packaging materials is described in this study. Using attenuated total internal reflection Fourier transform infrared spectroscopic imaging, suspect tablet coating and core formulations as well as multi-layered foil safety seals, bottle labels, and cigarette tear tapes were analyzed and compared directly with those of a stored authentic product. The approach was effective for obtaining molecular information from structures as small as 6 µm.

The Advantages of an Attenuated Total Internal Reflection Infrared Microspectroscopic Imaging Technique for the Analysis of Polymer Laminates.

Until recently, the analysis of polymer laminates using infrared microspectroscopy involved the painstaking separation of individual layers by dissection or by obtaining micrometer thin cross-sections. The latter usually requires the expertise of an individual trained in microtomy and even then, the very structure of the laminate could affect the outcome of the spectral results. The recent development of attenuated total internal reflection (ATR) infrared microspectroscopy imaging has provided a new avenue for the analysis of these multilayer structures. This report compares ATR infrared microspectroscopy imaging with conventional transmission infrared microspectroscopy imaging. The results demonstrate that the ATR method offers improved spatial resolution, eliminates a variety of competing optical processes, and requires minimal sample preparation relative to transmission measurements. These advantages were illustrated using a polymer laminate consisting of 11 different layers whose thickness ranged in size from 4-20 µm. The spatial resolution achieved by using an ATR-FTIR (Fourier transform infrared spectroscopy) imaging technique was diffraction limited. Contrast in the ATR images was enhanced by principal component analysis.

Simultaneous assessment of heart and lungs with gated high-pitch ultra-low dose chest CT using artificial intelligence-based calcium scoring.

Purpose: The combined testing for coronary artery and pulmonary diseases is of clinical interest as risk factors are shared. In this study, a novel ECG-gated tin-filtered ultra-low dose chest CT protocol (GCCT) for integrated heart and lung acquisition and the applicability of artificial intelligence (AI)-based coronary artery calcium scoring were assessed. Methods: In a clinical registry of 10481 patients undergoing heart and lung CT, GCCT was applied in 44 patients on a dual-source CT. Coronary calcium scans (CCS) with 120 kVp, 100 kVp, and tin-filtered 100 kVp (Sn100) of controls, matched with regard to age, sex, and body-mass index, were retrieved from the registry (ntotal=176, 66.5 (59.4-74.0) years, 52 men). Automatic tube current modulation was used in all scans. In 20 patients undergoing GCCT and Sn100 CCS, Agatston scores were measured both semi-automatically by experts and by AI, and classified into six groups (0, <10, <100, <400, <1000, ≥1000). Results: Effective dose decreased significantly from 120 kVp CCS (0.50 (0.41-0.61) mSv) to 100 kVp CCS (0.34 (0.26-0.37) mSv) to Sn100 CCS (0.14 (0.11-0.17) mSv). GCCT showed higher values (0.28 (0.21-0.32) mSv) than Sn100 CCS but lower than 120 kVp and 100 kVp CCS (all p < 0.05) despite greater scan length. Agatston scores correlated strongly between GCCT and Sn100 CCS in semi-automatic and AI-based measurements (both ρ = 0.98, p < 0.001) resulting in high agreement in Agatston score classification (κ = 0.97, 95% CI 0.92-1.00; κ = 0.89, 95% CI 0.79-0.99). Regarding chest findings, further diagnostic steps were recommended in 28 patients. Conclusions: GCCT allows for reliable coronary artery disease and lung cancer screening with ultra-low radiation exposure. GCCT-derived Agatston score shows excellent agreement with standard CCS, resulting in equivalent risk stratification.

Human AI Teaming for Coronary CT Angiography Assessment: Impact on Imaging Workflow and Diagnostic Accuracy.

As the number of coronary computed tomography angiography (CTA) examinations is expected to increase, technologies to optimize the imaging workflow are of great interest. The aim of this study was to investigate the potential of artificial intelligence (AI) to improve clinical workflow and diagnostic accuracy in high-volume cardiac imaging centers. A total of 120 patients (79 men; 62.4 (55.0-72.7) years; 26.7 (24.9-30.3) kg/m2) undergoing coronary CTA were randomly assigned to a standard or an AI-based (human AI) coronary analysis group. Severity of coronary artery disease was graded according to CAD-RADS. Initial reports were reviewed and changes were classified. Both groups were similar with regard to age, sex, body mass index, heart rate, Agatston score, and CAD-RADS. The time for coronary CTA assessment (142.5 (106.5-215.0) s vs. 195.0 (146.0-265.5) s; p < 0.002) and the total reporting time (274.0 (208.0-377.0) s vs. 350 (264.0-445.5) s; p < 0.02) were lower in the human AI than in the standard group. The number of cases with no, minor, or CAD-RADS relevant changes did not differ significantly between groups (52, 7, 1 vs. 50, 8, 2; p = 0.80). AI-based analysis significantly improves clinical workflow, even in a specialized high-volume setting, by reducing CTA analysis and overall reporting time without compromising diagnostic accuracy.

Connexin Mutants Cause Cataracts Through Deposition of Apatite.

Cataracts are lens opacities that are among the most common causes of blindness. It is commonly believed that cataracts develop through the accumulation of damage to lens proteins. However, recent evidence suggests that cataracts can result from calcium ion accumulation and the precipitation of calcium-containing salts. To test for the presence of precipitates and to identify their components, we studied the lenses of mice that develop cataracts due to mutations of connexin46 and connexin50. Micro-computed tomography showed the presence of radio-dense mineral in the mutant lenses, but not in wild-type lenses. Three-dimensional reconstructions of the scans showed that the distribution of the radio-dense mineral closely paralleled the location and morphology of the cataracts. The mutant lens homogenates also contained insoluble particles that stained with Alizarin red (a dye that stains Ca2+ deposits). Using attenuated total internal reflection micro-Fourier transform infrared spectroscopy, we identified the mineral as calcium phosphate in the form of apatite. Taken together, these data support the novel paradigm that cataracts are formed through pathological mineralization within the lens.

Factors influencing the safety of outpatient coronary CT angiography: a clinical registry study.

OBJECTIVES: Since the safety of coronary CT angiography (CTA) is of great importance, especially with regard to widening indications and increasing morbidity, the aim of this study was to assess influencing factors. METHODS: Patients undergoing coronary CTA in a third-generation dual-source CT in a radiological centre were included in a clinical registry. Up to 20 mg metoprolol was administered intravenously to attain a heart rate ≤65/min. Glyceryl trinitrate (GTN) was administered in doses of 0.8 mg and 0.4 mg. Blood pressure was measured before the administration and after the CTA. RESULTS: Out of 5500 consecutive patients (3194 men, 62.3 (54.9-70.0) years), adverse events occurred in 68 patients (1.2%) with mild anaphylactoid reactions (0.4%), vasovagal symptoms (0.3%) and extravasation (0.3%) being most frequent. Anti-allergic drugs were given in 17 patients, atropine in 3 patients and volume in 1 patient. Drug administration resulted in a significant mean arterial pressure decline (96.0 (88.3-106.0) vs 108.7 (99.7-117.3) mmHg; p<0.001). Patients who suffered systolic blood pressure drops >20 mmHg or >40 mmHg were older (66.5 (58.6-73.3) vs 60.5 (53.6-68.3) years; 70.2 (63.3-76.5) vs 62.1 (54.7-69.6) years), more often male (65.1% vs 54.4%; 68.9% vs 57.3%) and had higher Agatston score equivalents (83.0 (2.0-432.0) vs 15.0 (0.0-172.0); 163.0 (16.3-830.8) vs 25.0 (0.0-220.0); all p<0.001). GTN dose reduction lowered the fraction of patients suffering from blood pressure drops >20 mmHg or >40 mmHg from 34.5% to 27.4% and from 6.1% to 3.5% (both p<0.001), respectively. The proportion of coronary segments with impaired image quality did not differ significantly. CONCLUSIONS: Coronary CTA with intravenous beta-blocker administration is a safe procedure in an outpatient setting as adverse events are rare and mostly mild. Reduced GTN doses can further improve safety by lowering the rate of significant blood pressure drops, which occurred especially in elderly men with increased plaque burden. TRIAL REGISTRATION NUMBER: NCT03815123.

Analysis of counterfeit pharmaceutical tablet cores utilizing macroscopic infrared spectroscopy and infrared spectroscopic imaging.

Advantages and limitations of analyzing authentic and counterfeit pharmaceutical tablets with both macro (nonimaging) attenuated total internal reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and micro ATR-FT-IR spectroscopic imaging have been evaluated. The results of this study demonstrated that micro ATR imaging was more effective for extracting formulation information (sourcing), whereas a macro ATR approach was better suited for counterfeit detection (screening). More importantly, this study demonstrated that a thorough analysis of the counterfeit core can be achieved by combining the results of both techniques.

Short-Time Changes in Coronary Artery Plaques Assessed by Follow-Up Coronary CT Angiography-Characteristics and Impact on Patient Management.

Background: Coronary artery disease (CAD) shows a chronic but heterogeneous clinical course. Coronary CT angiography (CTA) allows for the visualization of the entire coronary tree and the detection of early stages of CAD. The aim of this study was to assess short-time changes in non-calcified and mixed plaques and their clinical impact using coronary CTA in a real-world setting. Methods: Between 11/2014 and 07/2019, 6,701 patients had a coronary CTA with a third-generation dual-source CT, of whom 77 patients (57 males, 63.8 ± 10.8 years) with a chronic CAD received clinically indicated follow-up CTA. Non-calcified and mixed plaques were analyzed in 1,211 coronary segments. Patients were divided into groups: stable, progressive, or regressive plaques. Results: Within the follow-up period of 22.3 ± 10.4 months, 44 patients (58%) showed stable plaques, 27 (36%) showed progression, 5 (7%) showed regression. One patient was excluded due to an undetermined CAD course showing both, progressive and regressive plaques. Age did not differ significantly between groups. Patients with plaque regression were predominantly female (80 vs. 20%), whereas patients showing progression were mainly male (85 vs. 15%; p < 0.01 for both). Regression was only observed in patients with mild CAD or one-vessel disease. The follow-up CTA led to changes in patient management in the majority of subjects (n = 50; 66%). Conclusions: Changes in coronary artery plaques can be observed within a short period resulting in an adjustment of the clinical management in the majority of CAD patients. Follow-up coronary CTA renders the non-invasive assessment of plaque development possible and allows for an individualized diagnostics and therapy optimization.

Multimodal imaging reveals a unique autofluorescence signature of Randall's plaque.

Kidney stones frequently develop as an overgrowth on Randall's plaque (RP) which is formed in the papillary interstitium. The organic composition of RP is distinct from stone matrix in that RP contains fibrillar collagen; RP in tissue has also been shown to have two proteins that are also found in stones, but otherwise the molecular constituents of RP are unstudied. We hypothesized that RP contains unique organic molecules that can be differentiated from the stone overgrowth by fluorescence. To test this, we used micro-CT-guided polishing to expose the interior of kidney stones for multimodal imaging with multiphoton, confocal and infrared microscopy. We detected a blue autofluorescence signature unique to RP, the specificity of which was also confirmed in papillary tissue from patients with stone disease. High-resolution mineral mapping of the stone also showed a transition from the apatite within RP to the calcium oxalate in the overgrowth, demonstrating the molecular and spatial transition from the tissue to the urine. This work provides a systematic and practical approach to uncover specific fluorescence signatures which correlate with mineral type, verifies previous observations regarding mineral overgrowth onto RP and identifies a novel autofluorescence signature of RP demonstrating RP's unique molecular composition.

Renal histopathology and crystal deposits in patients with small bowel resection and calcium oxalate stone disease.

We present here the anatomy and histopathology of kidneys from 11 patients with renal stones following small bowel resection, including 10 with Crohn's disease and 1 resection in infancy for unknown cause. They presented predominantly with calcium oxalate stones. Risks of formation included hyperoxaluria (urine oxalate excretion greater than 45 mg per day) in half of the cases, and acidic urine of reduced volume. As was found with ileostomy and obesity bypass, inner medullary collecting ducts (IMCDs) contained crystal deposits associated with cell injury, interstitial inflammation, and papillary deformity. Cortical changes included modest glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Randall's plaque (interstitial papillary apatite) was abundant, with calcium oxalate stone overgrowth similar to that seen in ileostomy, idiopathic calcium oxalate stone formers, and primary hyperparathyroidism. Abundant plaque was compatible with the low urine volume and pH. The IMCD deposits all contained apatite, with calcium oxalate present in three cases, similar to findings in patients with obesity bypass but not an ileostomy. The mechanisms for calcium oxalate stone formation in IMCDs include elevated urine and presumably tubule fluid calcium oxalate supersaturation, but a low calcium to oxalate ratio. However, the mechanisms for the presence of IMCD apatite remain unknown.

Discrepancy Between Stone and Tissue Mineral Type in Patients with Idiopathic Uric Acid Stones.

Objectives: To describe the papillary pathology found in uric acid (UA) stone formers, and to investigate the mineral form of tissue deposits. Materials and Methods: We studied eight UA stone formers treated with percutaneous nephrolithotomy. Papillae were imaged intraoperatively using digital endoscopy, and cortical and papillary biopsies were taken. Biopsies were analyzed by light microscopy, micro-CT, and microinfrared spectroscopy. Results: As expected, urine pH was generally low. UA supersaturation exceeded one in all but one case, compatible with the stone material. By intraoperative imaging, the renal papillae displayed a heterogeneous mixture of plaque and plugging, ranging from normal to severe. All patients had mineral in ducts of Bellini and inner medullary collecting ducts, mainly apatite with lesser amounts of urate and/or calcium oxalate in some specimens. Papillary and cortical interstitial tissue injury was modest despite the tubule plugging. No instance was found of a stone growing attached to either plaque or plugs. Conclusions: UA stone formers resemble those with ileostomy in having rather low urine pH while forming tubule plugs that contain crystals that can only form at pH values above those of their bulk urine. This discrepancy between tissue mineral deposits and stone type suggests that local tubular pH exceeds that of the bulk urine, perhaps because of localized tubule injury. The manner in which UA stones form and the discordance between tubule crystals and stone type remain open research questions.

Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease.

The major risk factor for kidney stone disease is idiopathic hypercalciuria. Recent evidence implicates a role for defective calcium reabsorption in the renal proximal tubule. We hypothesized that claudin-2, a paracellular cation channel protein, mediates proximal tubule calcium reabsorption. We found that claudin-2-null mice have hypercalciuria due to a primary defect in renal tubule calcium transport and papillary nephrocalcinosis that resembles the intratubular plugs in kidney stone formers. Our findings suggest that a proximal tubule defect in calcium reabsorption predisposes to papillary calcification, providing support for the vas washdown hypothesis. Claudin-2-null mice were also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting that this was due to reduced intestinal calcium secretion. Common genetic variants in the claudin-2 gene were associated with decreased tissue expression of claudin-2 and increased risk of kidney stones in 2 large population-based studies. Finally, we describe a family in which males with a rare missense variant in claudin-2 have marked hypercalciuria and kidney stone disease. Our findings indicate that claudin-2 is a key regulator of calcium excretion and a potential target for therapies to prevent kidney stones.

Intra-tubular deposits, urine and stone composition are divergent in patients with ileostomy.

Patients with ileostomy typically have recurrent renal stones and produce scanty, acidic, sodium-poor urine because of abnormally large enteric losses of water and sodium bicarbonate. Here we used a combination of intra-operative digital photography and biopsy of the renal papilla and cortex to measure changes associated with stone formation in seven patients with ileostomy. Papillary deformity was present in four patients and was associated with decreased estimated glomerular filtration rates. All patients had interstitial apatite plaque, as predicted from their generally acid, low-volume urine. Two patients had stones attached to plaque; however, all patients had crystal deposits that plugged the ducts of Bellini and inner medullary collecting ducts (IMCDs). Despite acid urine, all crystal deposits contained apatite, and five patients had deposits of sodium and ammonium acid urates. Stones were either uric acid or calcium oxalate as predicted by supersaturation, however, there was a general lack of supersaturation for calcium phosphate as brushite, sodium, or ammonium acid urate because of the overall low urine pH. This suggests that local tubular pH exceeds that of bulk urine. Despite low urine pH, patients with an ileostomy resemble those with obesity bypass, in whom IMCD apatite crystal plugs are found. They are, however, unlike these bypass patients in having interstitial apatite plaque. IMCD plugging with sodium and ammonium acid urate has not been found previously and appears to correlate with formation of uric acid stones.

Histopathology and surgical anatomy of patients with primary hyperparathyroidism and calcium phosphate stones.

Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of Bellini, and plugging with apatite deposits of the inner medullary collecting ducts and ducts of Bellini. Some of the papillae in two of the patients contained plentiful large interstitial deposits of Randall's plaque and where the deposits were most plentiful we found overgrowth of the attached stones. Hence, this disease combines features previously described in brushite stone formers--dilation, plugging of ducts and papillary deformity--with the interstitial plaque and stone overgrowth characteristic of routine idiopathic calcium oxalate stone formers, suggesting that these two patterns can coexist in a single patient.

Randall's plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle.

Our purpose here is to test the hypothesis that Randall's plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non-stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non-stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated.

Prism-based infrared spectrographs using modern-day detectors.

A comparison of prism-based spectrographs to grating-based spectrographs is made when each of the systems is coupled to a modern-day liquid-nitrogen-cooled photovoltaic array detector. A comparison of the systems is also made using a room-temperature microbolometer array detector. Finally, infrared microspectroscopy of samples whose size is approximately 10 micrometers will be demonstrated using a prism spectrograph outfitted with both types of detectors. The results of the study show that prism-based spectrographs offer an economical alternative to grating-based systems when spectral coverage is more critical than spectral resolution. The results also demonstrate that spectra with good signal-to-noise ratios can be collected on any of the systems with a total integration time of 10 seconds or less.

Limits of the possible: diagnostic image quality in coronary angiography with third-generation dual-source CT.

BACKGROUND: The usage of coronary CT angiography (CTA) is appropriate in patients with acute or chronic chest pain; however the diagnostic accuracy may be challenged with increased Agatston score (AS), increased heart rate, arrhythmia and severe obesity. Thus, we aim to determine the potential of the recently introduced third-generation dual-source CT (DSCT) for CTA in a 'real-life' clinical setting. METHODS: Two hundred and sixty-eight consecutive patients (age: 67 ± 10 years; BMI: 27 ± 5 kg/m²; 61% male) undergoing clinically indicated CTA with DSCT were included in the retrospective single-center analysis. A contrast-enhanced volume dataset was acquired in sequential (SSM) (n = 151) or helical scan mode (HSM) (n = 117). Coronary segments were classified in diagnostic or non-diagnostic image quality. A subset underwent invasive angiography to determine the diagnostic accuracy of CTA. RESULTS: SSM (96.8 ± 6%) and HSM (97.5 ± 8%) provided no significant differences in the overall diagnostic image quality. However, AS had significant influence on diagnostic image quality exclusively in SSM (B = 0.003; p = 0.0001), but not in HSM. Diagnostic image quality significantly decreased in SSM in patients with AS ≥2,000 (p = 0.03). SSM (sensitivity: 93.9%; specificity: 96.7%; PPV: 88.6%; NPV: 98.3%) and HSM (sensitivity: 97.4%; specificity: 94.3%; PPV: 86.0%; NPV: 99.0%) provided comparable diagnostic accuracy (p = n.s.). SSM yielded significantly lower radiation doses as compared to HSM (2.1 ± 2.0 vs. 5.1 ± 3.3 mSv; p = 0.0001) in age and BMI-matched cohorts. CONCLUSION: SSM in third-generation DSCT enables significant dose savings and provides robust diagnostic image quality in patients with AS ≤2000 independent of heart rate, heart rhythm or obesity.