Low-cost 3D printed lenses for brightfield and fluorescence microscopy.

We present the fabrication and implementation of low-cost optical quality 3D printed lenses, and their application as microscope objectives with different prescriptions. The imaging performance of the 3D printed lenses was benchmarked against commercially available optics including a 20 mm focal length 12.7 mm diameter NBK-7 plano-convex lens used as a low magnification objective, and a separate high magnification objective featuring three 6 mm diameter NBK-7 lenses with different positive and negative focal lengths. We describe the design and manufacturing processes to produce high-quality 3D printed lenses. We tested their surface quality using a stylus profilometer, showing that they conform to that of commercial glass counterpart lenses. The 3D printed lenses were used as microscope objectives in both brightfield and epi-fluorescence imaging of specimens including onion, cyanobacteria, and variegated Hosta leaves, demonstrating a sub-cellular resolution performance obtained with low-cost 3D printed optical elements within brightfield and fluorescence microscopy.

Cold-atom shaping with MEMS scanning mirrors.

We demonstrate the integration of micro-electro-mechanical-systems (MEMS) scanning mirrors as active elements for the local optical pumping of ultra-cold atoms in a magneto-optical trap. A pair of MEMS mirrors steer a focused resonant beam through a cloud of trapped atoms shelved in the F = 1 ground-state of 87Rb for spatially selective fluorescence of the atom cloud. Two-dimensional control is demonstrated by forming geometrical patterns along the imaging axis of the cold atom ensemble. Such control of the atomic ensemble with a microfabricated mirror pair could find applications in single atom selection, local optical pumping, and arbitrary cloud shaping. This approach has significant potential for miniaturization and in creating portable control systems for quantum optic experiments.

Semi-automated volumetry of pulmonary nodules: Intra-individual comparison of standard dose and chest X-ray equivalent ultralow dose chest CT scans.

PURPOSE: To assess the performance of semi-automated volumetry of solid pulmonary nodules on single-energy tin-filtered ultralow dose (ULD) chest CT scans at a radiation dose equivalent to chest X-ray relative to standard dose (SD) chest CT scans and assess the impact of kernel and iterative reconstruction selection. METHODS: Ninety-four consecutive patients from a prospective single-center study were included and underwent clinically indicated SD chest CT (1.9 ± 0.8 mSv) and additional ULD chest CT (0.13 ± 0.01 mSv) in the same session. All scans were reconstructed with a soft tissue (Br40) and lung (Bl64) kernel as well as with Filtered Back Projection (FBP) and Iterative Reconstruction (ADMIRE-3 and ADMIRE-5). One hundred and forty-eight solid pulmonary nodules were identified and analysed by semi-automated volumetry on all reconstructions. Nodule volumes were compared amongst all reconstructions thereby focusing on the agreement between SD and ULD scans. RESULTS: Nodule volumes ranged from 58.5 (28.8-126) mm3 for ADMIRE-5 Br40 ULD reconstructions to 72.5 (39-134) mm3 for FBP Bl64 SD reconstructions with significant differences between reconstructions (p < 0.001). Interscan agreement of volumes between two given reconstructions ranged from ICC = 0.605 to ICC = 0.999. Between SD and ULD scans, agreement of nodule volumes was highest for FBP Br40 (ICC = 0.995), FBP Bl64 (ICC = 0.939) and ADMIRE-5 Bl64 (ICC = 0.994) reconstructions. ADMIRE-3 reconstructions exhibited reduced interscan agreement of nodule volumes (ICCs from 0.788 - 0.882). CONCLUSIONS: The interscan agreement of node volumes between SD and ULD is high depending on the choice of kernel and reconstruction algorithm. However, caution should be exercised when comparing two image series that were not identically reconstructed.

Miniaturized structured illumination microscopy using two 3-axis MEMS micromirrors.

We present the development and performance characterisation of a novel structured illumination microscope (SIM) in which the grating pattern is generated using two optical beams controlled via 2 micro-electro-mechanical system (MEMS) three-axis scanning micromirrors. The implementation of MEMS micromirrors to accurately and repeatably control angular, radial and phase positioning delivers flexible control of the fluorescence excitation illumination, with achromatic beam delivery through the same optical path, reduced spatial footprint and cost-efficient integration being further benefits. Our SIM architecture enables the direct implementation of multi-color imaging in a compact and adaptable package. The two-dimensional SIM system approach is enabled by a pair of 2 mm aperture electrostatically actuated three-axis micromirrors having static angular tilt motion along the x- and y-axes and static piston motion along the z-axis. This allows precise angular, radial and phase positioning of two optical beams, generating a fully controllable spatial interference pattern at the focal plane by adjusting the positions of the beam in the back-aperture of a microscope objective. This MEMS-SIM system was applied to fluorescent bead samples and cell specimens, and was able to obtain a variable lateral resolution improvement between 1.3 and 1.8 times the diffraction limited resolution.

Tunable Wide-Field Illumination and Single-Molecule Photoswitching with a Single MEMS Mirror.

Homogeneous illumination in single-molecule localization microscopy (SMLM) is key for the quantitative analysis of super-resolution images. Therefore, different approaches for flat-field illumination have been introduced as alternative to the conventional Gaussian illumination. Here, we introduce a single microelectromechanical systems (MEMS) mirror as a tunable and cost-effective device for adapting wide-field illumination in SMLM. In flat-field mode the MEMS allowed for consistent SMLM metrics across the entire field of view. Employing single-molecule photoswitching, we developed a simple yet powerful routine to benchmark different illumination schemes on the basis of local emitter brightness and ON-state lifetime. Moreover, we propose that tuning the MEMS beyond optimal flat-field conditions enables to study the kinetics of photoswitchable fluorophores within a single acquisition.

MEMS enabled miniaturized light-sheet microscopy with all optical control.

We have designed and implemented a compact, cost-efficient miniaturised light-sheet microscopy system based on optical microelectromechanical systems scanners and tunable lenses. The system occupies a footprint of 20 × 28 × 13 cm3 and combines off-the-shelf optics and optomechanics with 3D-printed structural and optical elements, and an economically costed objective lens, excitation laser and camera. All-optical volume scanning enables imaging of 435 × 232 × 60 µm3 volumes with 0.25 vps (volumes per second) and minimum lateral and axial resolution of 1.0 µm and 3.8 µm respectively. An open-top geometry allows imaging of samples on flat bottomed holders, allowing integration with microfluidic devices, multi-well plates and slide mounted samples, with applications envisaged in biomedical research and pre-clinical settings.

Comparison of virtual non-contrast dual-energy CT and a true non-contrast CT for contouring in radiotherapy of 3D printed lung tumour models in motion: a phantom study.

OBJECTIVES: This work aims to investigate whether virtual non-contrast (VNC) dual-energy CT(DECT) of contrasted lung tumours can be used as an alternative for true non-contrast (TNC) images in radiotherapy. Two DECT techniques and a TNC CT were compared and influences on gross tumour volume (GTV) volume and CT number from motion artefacts in three-dimensional printed lung tumour models (LTM) in amotion phantom were examined. METHODS: Two spherical LTMs (diameter 3.0 cm) with different inner shapes were created in a three-dimensional printer. The inner shapes contained water or iodine (concentration 5 mg ml-1) and were scanned with a dual-source DECT (ds-DECT), single-source sequential DECT (ss-DECT) and TNC CT in a respiratory motion phantom (15 breaths/min, amplitude 1.5 cm). CT number and volume of LTMs were measured. Therefore, two GTVs were contoured. RESULTS: Deviations in GTV volume (outer shape) of LTMs in motion for contrast-enhanced ss-DECT and ds-DECT VNC images compared to TNC images are not significant (p > 0.05). Relative GTV volume and CT number deviations (inner shapes) of LTMs in motion were 6.6 ± 0.6% and 104.4 ± 71.2 HU between ss-DECT and TNC CT and -8.4 ± 10.6% and 25.5 ± 58.5 HU between ds-DECT and TNC, respectively. CONCLUSION: ss-DECT VNC images could not sufficiently subtract iodine from water in LTMs inmotion, whereas ds-DECT VNC images might be a valid alternative to a TNC CT. ADVANCES IN KNOWLEDGE: ds-DECT provides a contrasted image for contouring and a non-contrasted image for radiotherapy treatment planning for LTM in motion.

Multi-layer light trapping structures for enhanced solar collection.

Light trapping is a commonly used technique for enhancing the efficiency of solar collection in many photovoltaic (PV) devices. In this paper, we present the design of multi-layer light trapping structures that can potentially be retrofitted, or directly integrated, onto crystalline or amorphous silicon solar panels for enhanced optical collection at normal and extreme angle of incidence. This approach can improve the daily optical collection performance of solar panel with and without internally integrated light trapping structure by up to 7.18% and 159.93%, respectively. These improvements predict an enhancement beyond many research level and commercially deployed light trapping technologies. We further enhance this performance by combining our multi-layer optics with high refractive index materials to achieve a daily optical collection of up to 32.20% beyond leading light trapping structures. Our additive light trapping designs could enable the upgradeability of older PV technologies and can be tailored to optimally operate at unique angular ranges for building exteriors or over a wide range of incidence angle for applications such as unmanned aerial vehicles.

Influence of contrast material density and kV setting on detectability of calcified plaques on coronary CT angiography.

PURPOSE: To analyze the impact of tube potential and iodine concentration on the visibility of calcified plaques in coronary computed tomography angiography (cCTA). METHODS & MATERIALS: 164 consecutive patients (65.9 % men and a mean age of 57.1 ±â€¯11.3 years) with suspected coronary artery disease underwent calcium scoring (CaSc) scan followed by cCTA with topogram-based automated tube voltage selection (70 kV, 80 kV, 90 kV, 100 kV or 120 kV). In 127 Patients (HC), we injected 50 mL of contrast material (CM) with a concentration of 400 mg iodine per ml and in 37 patients (LC) 50 mL iodine concentration of 280 mg/mL. Sensitivity of cCTA for detecting calcified plaques was calculated with CaSc serving as gold standard. Density of CM enhanced coronary vessels and calcified plaques were quantified by region-of-interest (ROI) measurements in unenhanced and cCTA image series. RESULTS: Overall sensitivity of cCTA to detect calcified plaques was significantly higher using LC compared to HC (79 % vs. 73 %; p = 0.0035). The impact of LC was impressive at 70 kV with an improved sensitivity of 70 % vs. 57.1 % in HC (p = 0.0082). Furthermore, density values of HC enhanced coronary vessels exceeded those of calcified plaques, especially at low kV levels. In LC, except for the 70 kV setting, higher density values were shown for calculi than enhanced vessels. CONCLUSION: Low kV cCTA in routine using highly concentrated CM leads to reduced calcified plaque perceptibility and hence potentially underestimation of stenosis. Thus, low kV cCTA using CM with lower iodine concentration is necessary. In addition, a dose reduction up to 77.7 % can also be benefited.

Multi-element lenslet array for efficient solar collection at extreme angles of incidence.

Photovoltaics (PV) are a versatile and compact route to harness solar power. One critical challenge with current PV is preserving the optimal panel orientation angle with respect to the sun for efficient energy conversion. We experimentally demonstrate a bespoke multi-element lenslet array that allows for an increased power collection over a wide field of view by increasing the effective optical interaction length by up to 13 times specifically at large angles of incidence. This design can potentially be retrofitted onto already deployed amorphous silicon solar panels to yield an increased daily power generation by a factor of 1.36 for solar equivalent illumination. We 3D printed an optical proof of concept multi-element lenslet array to confirm an increase in power density for optical rays incident between 40 and 80 degrees. Our design indicates a novel optical approach that could potentially enable increased efficient solar collection in extreme operating conditions such as on the body of planes or the side of buildings.

Chest X-ray Dose Equivalent Low-dose CT with Tin Filtration: Potential Role for the Assessment of Pectus Excavatum.

RATIONALE AND OBJECTIVES: To determine the value of chest CT with tin filtration applying a dose equivalent to chest x-ray for the assessment of the Haller index for evaluation of pectus excavatum. MATERIALS AND METHODS: Two hundred seventy-two patients from a prospective single center study were included and underwent a clinical standard dose chest CT (effective dose 1.8 ± 0.7 mSv) followed by a low-dose CT (0.13 ± 0.01 mSv) in the same session. Two blinded readers independently evaluated all data sets. Image quality for bony chest wall assessment was noted. Radiologists further assessed (a) transverse thoracic diameter, (b) anteroposterior thoracic diameter, and calculated (c) Haller index by dividing transverse diameter by anteroposterior diameter. The agreement of both readers in standard dose and low-dose CT was assessed using Lin's concordance correlation coefficient (pc). RESULTS: Subjective image quality was lower for low dose compared to standard dose CT images by both readers (p < 0.001). In total, 99% (n = 540) of low-dose CT scans were rated as diagnostic for bony chest wall assessment by both readers. There was a high agreement for assessment of transverse diameter, anteroposterior diameter and Haller index comparing both readers in standard dose and low-dose CT with pc values indicating substantial agreement (i.e., 0.95> and ≤0.99) in 12/18 (67%) and almost perfect agreement (i.e., >0.99) in 6/18 (33%). CONCLUSION: Our study suggests that low-dose CT with tin filtration applying a radiation dose equivalent to a plain chest X-ray is excellent for assessing the Haller index.

Lung cancer screening with submillisievert chest CT: Potential pitfalls of pulmonary findings in different readers with various experience levels.

PURPOSE: To assess the interreader variability of submillisievert CT for lung cancer screening in radiologists with various experience levels. METHOD: Six radiologists with different degrees of clinical experience in radiology (range, 1-15 years), rated 100 submillisievert CT chest studies as either negative screening finding (no nodules, benign nodules, nodules <5 mm), indeterminate finding (nodules 5-10 mm), positive finding (nodules >10 mm). Each radiologist interpreted scans randomly ordered and reading time was recorded. Interobserver agreement was assessed with ak statistic. Reasons for differences in nodule classification were analysed on a case-by-case basis. Reading time was correlated with reader experience using Pearson correlation (r). RESULTS: The overall interobserver agreement between all readers was moderate (k = 0.454; p < 0.001). In 57 patients, all radiologists agreed on the differentiation of negative and indeterminate/positive finding. In 64 cases disagreement between readers led to different nodule classification. In 8 cases some readers rated the nodule as benign, whereas others scored the case as positive. Overall, disagreement in nodule classification was mostly due to failure in identification of target lesion (n = 40), different lesion measurement (n = 44) or different classification (n = 26). Mean overall reading time per scan was of 2 min 2 s (range: 7s-7 min 45 s) and correlated with reader-experience (r = -0.824). CONCLUSIONS: Our study showed substantial interobserver variability for the detection and classification of pulmonary nodules in submillisievert CT. This highlights the importance for careful standardisation of screening programs with the objective of harmonizing efforts of involved radiologists across different institutions by defining and assuring quality standards.

TIP30 counteracts cardiac hypertrophy and failure by inhibiting translational elongation.

Pathological cardiac overload induces myocardial protein synthesis and hypertrophy, which predisposes to heart failure. To inhibit hypertrophy therapeutically, the identification of negative regulators of cardiomyocyte protein synthesis is needed. Here, we identified the tumor suppressor protein TIP30 as novel inhibitor of cardiac hypertrophy and dysfunction. Reduced TIP30 levels in mice entailed exaggerated cardiac growth during experimental pressure overload, which was associated with cardiomyocyte cellular hypertrophy, increased myocardial protein synthesis, reduced capillary density, and left ventricular dysfunction. Pharmacological inhibition of protein synthesis improved these defects. Our results are relevant for human disease, since we found diminished cardiac TIP30 levels in samples from patients suffering from end-stage heart failure or hypertrophic cardiomyopathy. Importantly, therapeutic overexpression of TIP30 in mouse hearts inhibited cardiac hypertrophy and improved left ventricular function during pressure overload and in cardiomyopathic mdx mice. Mechanistically, we identified a previously unknown anti-hypertrophic mechanism, whereby TIP30 binds the eukaryotic elongation factor 1A (eEF1A) to prevent the interaction with its essential co-factor eEF1B2 and translational elongation. Therefore, TIP30 could be a therapeutic target to counteract cardiac hypertrophy.

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Enhanced radiation exposure associated with anterior-posterior x-ray tube position in young women undergoing cardiac computed tomography.

Given the current increase in the incidence of coronary artery disease in younger women as well as the high lifetime risk of developing an x-ray-induced malignancy in this population, we aimed at assessing chest radiation in 206 women ≤55 years old undergoing coronary calcium scoring (CACS) by using a Monte Carlo simulation tool. Our data indicate that the simulated radiation dose of the female breast during CACS depends substantially on the starting position of the x-ray tube, with an almost 2 times excess of breast radiation exposure being measured during anterior-posterior tube positioning. Thus, an additional technical feature taking into account the position of the x-ray tube when acquisition is triggered might be an important tool to reduce radiation exposure of the female breast during CACS.

Various effects of AAV9-mediated ßARKct gene therapy on the heart in dystrophin-deficient (mdx) mice and δ-sarcoglycan-deficient (Sgcd-/-) mice.

So far effective strategies to treat cardiomyopathy in patients with muscular dystrophies are still not clearly defined. Previously, treatment with ß-blockers showed beneficial effects on the development of cardiomyopathy in dystrophin-deficient (mdx) mice, but not in δ-sarcoglycan-deficient (Sgcd-/-) mice. We therefore aimed to study a more specific approach to target maladaptive ß-adrenergic signalling in these mice. It has been shown that lowering cardiac G-protein-coupled-receptor-kinase-2 (GRK2) activity with ßARKct expression, a peptide inhibitor of protein-coupled-receptor-kinase-2 (GRK2), results in improvement of heart failure in several different animal models. We therefore investigated whether adeno-associated virus type 9 (AAV9)-mediated gene delivery of ßARKct, could ameliorate cardiac pathology in mdx and Sgcd-/- mice. We found that long-term treatment with AAV9- ßARKct-cDNA with a cardiac-specific promoter significantly improves left ventricular systolic function and reduces myocardial hypertrophy in mdx mice, whereas only mild beneficial effects on cardiac function is observed in Sgcd-/- mice. Interestingly, in contrast to mdx mice neither GRK2 nor nuclear-factor-kappaB (NFκB) were upregulated in Sgcd-/- mice. Taken together, effectiveness of AAV-mediated ßARKct therapy may vary between different genetic mutations and presumably depend on the state of adrenergic dysregulation mediated through the upregulation of GRK2.

Peak V'O2 is an independent predictor of survival in patients with cardiac amyloidosis.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) has repeatedly been reported to reliably predict adverse outcomes in different forms of heart failure. However, it has not been elucidated in detail in cardiac amyloidosis (CA). Therefore, we evaluated the predictive value of CPET parameters in patients with CA regarding disease severity and prediction of mortality. METHODS: Twenty-seven consecutive patients with CA were assessed noninvasively, including electrocardiography, echocardiography, CPET, and laboratory tests. Clinical data were correlated with CPET findings. Univariate and multivariate analyses were performed to evaluate predictors of mortality. RESULTS: Within median follow-up period of 38 (IQR 43) months 19 (70%) deaths occurred. Patient initially presented with signs and symptoms of congestive heart failure NYHA 3 (IQR 1), reduced exercise capacity (peak V'O2 15.2 mL/kg body weight) and inefficient ventilation in CPET (V'E/V'CO2 slope (30 (IQR 3)), markedly elevated cardiac biomarkers (NT-proBNP 1791 (IQR 3249) ng/mL) and echocardiographic signs of morphological (septum thickness 18 (IQR 6) mm) and functional cardiac involvement (TAPSE 19 (IQR 8) mm). Patients with peak V'O2 below median value presented with significantly longer QTc interval when compared to patients with peak V'O2 above the median. Further these patients tend to have more pronounced impairment of longitudinal function as indicated by lower MAPSE, TAPSE, and elevation of cardiac biomarkers. Multivariate analysis revealed peak V'O2 slope as the only independent predictor of survival. CONCLUSIONS: We identified reduced peak V'O2 as an independent predictor of mortality in patients with cardiac involvement in different forms of systemic amyloidosis.

Dynamic 4D-CT Angiography for Guiding Transarterial Chemoembolization: Impact on the Reduction of Contrast Material, Operator Radiation Exposure, Catheter Consumption, and Diagnostic Confidence.

PURPOSE: This study was carried out to investigate the impact of abdominal dynamic four-dimensional CT angiography (4D-CTA) for guiding transarterial chemoembolization (TACE) on the amount of contrast material used, operator radiation exposure, catheter consumption, and diagnostic confidence. MATERIALS AND METHODS: Written consent was waived for this IRB-approved retrospective study. 29 patients (20 men; mean age: 65.7 ±â€Š11.5 years) with malignant liver lesions underwent 4D-CTA, prior to initial TACE. Time-resolved volume-rendering technique (VRT), maximum-intensity projection (MIP), and multiplanar reconstruction (MPR) series were reconstructed, enabling a direct selective catheterization of the tumor-supplying artery without prior conventional digital subtraction angiography (DSA). 29 patients (16 men; mean age: 69.4 ±â€Š13.9) who underwent traditional TACE served as the control group. The amount of administered contrast media, operator radiation exposure, and catheter consumption during TACE were compared. Two radiologists assessed diagnostic confidence in the exclusion of portal vein thrombosis. RESULTS: 4D-CTA TACE resulted in a significant reduction in the amount of contrast media used, compared to traditional TACE (-61.0 ml/ -66.3 % intra-arterial, -12.8 ml/ -13.8 % overall; P < 0.001). The dose-area product indicating operator radiation exposure during intervention was reduced by 50.5 % (P < 0.001), and 0.7 fewer catheters on average were used (P = 0.063), while 4D-CTA data was available to guide TACE. Diagnostic confidence in the exclusion of portal vein thrombosis was significantly enhanced by 4D-CTA, compared to traditional DSA images (scores, 3.9 and 2.4, respectively; P < 0.001). CONCLUSION: Dynamic 4D-CTA enables TACE with a substantially reduced amount of contrast material, decreases operator radiation exposure, and increases diagnostic confidence in the exclusion of portal vein thrombosis. KEY POINTS: · 4D-CTA prior to TACE decreases the amount of utilized contrast material.. · The intra-arterial fraction of contrast media can be reduced by two-thirds.. · The risk of CIN may be decreased by means of 4D-CTA TACE.. · Operator radiation exposure is lower using 4D-CTA for guiding TACE.. · 4D-CTA portography allows for a higher diagnostic confidence than conventional DSA images.. CITATION FORMAT: · Albrecht MH, Vogl TJ, Wichmann JL et al. Dynamic 4D-CT Angiography for Guiding Transarterial Chemoembolization: Impact on the Reduction of Contrast Material, Operator Radiation Exposure, Catheter Consumption, and Diagnostic Confidence. Fortschr Röntgenstr 2018; 190: 513 - 520.

Ion Channel Dysfunctions in Dilated Cardiomyopathy in Limb-Girdle Muscular Dystrophy.

BACKGROUND: Limb-Girdle muscular dystrophies (LGMD) are a heritable group of genetically determined disorders with a primary involvement of the pelvic or shoulder girdle musculature with partially cardiac manifestation, such as dilated cardiomyopathy (DCM) and life-threatening tachyarrhythmia. We report here that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from a patient with LGMD2I and DCM associated with recurrent ventricular tachycardia displayed ion channel dysfunction and abnormality of calcium homeostasis. METHODS: Dermal fibroblasts obtained from a patient with LGMD2I harboring a fukutin-related protein gene mutation (826C>A; Leu276Ile) and 3 healthy donors were reprogrammed to hiPSCs. The hiPSCs were differentiated into cardiomyocytes and used for biological and electrophysiological studies. RESULTS: Compared with hiPSC cardiomyocytes from the healthy donors, the hiPSC cardiomyocytes from the patient exhibited abnormal action potentials characterized by reduced amplitude and upstroke velocity. The peak and late Na channel currents (INa) as well as the peak L-type calcium channel currents were significantly reduced. The expression of SCN5A and CACNA1C was reduced in DCM cardiomyocytes, consistent with reduction of INa and L-type calcium channel currents. In addition, the rapidly activating delayed rectifier potassium current (IKr) was reduced, whereas the transient outward current (Ito) and slowly activating delayed rectifier potassium current (IKs) were similar in DCM and control cardiomyocytes. Finally, a significant reduction of systolic and diastolic intracellular Ca2+ concentrations was detected in DCM cardiomyocytes. CONCLUSIONS: This study demonstrates that patient-specific hiPSC cardiomyocytes can recapitulate some phenotypic properties of LGMD2I with DCM and provide a platform for studies on the cardiac events in LGMD.