On-chip microlasers for biomolecular detection via highly localized deposition of a multifunctional phospholipid ink.

We report on a novel approach to realize on-chip microlasers, by applying highly localized and material-saving surface functionalization of passive photonic whispering gallery mode microresonators. We apply dip-pen nanolithography on a true three-dimensional structure. We coat solely the light-guiding circumference of pre-fabricated poly(methyl methacrylate) resonators with a multifunctional molecular ink. The functionalization is performed in one single fabrication step and simultaneously provides optical gain as well as molecular binding selectivity. This allows for a direct and flexible realization of on-chip microlasers, which can be utilized as biosensors in optofluidic lab-on-a-chip applications. In a proof-of-concept we show how this highly localized molecule deposition suffices for low-threshold lasing in air and water, and demonstrate the capability of the ink-lasers as biosensors in a biotin-streptavidin binding experiment.

Flexible coupling of high-Q goblet resonators for formation of tunable photonic molecules.

We report on a method for a highly flexible arrangement of polymeric high-Q whispering gallery mode resonators. Parallel on-chip fabricated goblet resonators are detached from the substrate by bonding a gold wire to the field-free center of their polymeric cavity. This enables the precise control of the resonator's spatial position. The modal spectrum of the detached resonator reveals preservation of its high optical quality. Manipulation of the resonators' position allows for designing coupled resonators geometries and tuning the coupling properties dynamically after batch fabrication. The properties of the modal spectrum evidence the successful optical coupling.

Differentiating cardiac amyloidosis and hypertrophic cardiomyopathy by use of three-dimensional speckle tracking echocardiography.

INTRODUCTION: Cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) are important differential diagnosis of left ventricular hypertrophy. The aim of this study was to investigate if three-dimensional (3D) speckle tracking-derived functional parameters enabled differentiation of CA and HCM by a disease-specific pattern. METHODS: Twelve patients with CA and 12 patients with HCM were included. CA and HCM were diagnosed by contrast-enhanced cardiovascular magnetic resonance (CMR). Three-dimensional speckle tracking echocardiography with wall motion analysis was performed for strain (radial [RS(%)], longitudinal [LS (-%)], and circumferential [CS (-%)]), rotation (ROT [degree]), and twist (TWT [degree]). Intergroup comparison included normalized values from 49 healthy volunteers. RESULTS: Averaged RS, LS, CS, ROT, and TWT were investigated at basal, midventricular, and apical levels. With some exceptions, 3D speckle tracking function parameters were mostly lower in the HCM and minimal in the CA group as compared to controls. Comparing CA and HCM, basal RS was significantly reduced in patients with amyloidosis (7.5 ± 19.7 vs. 22.3 ± 22.7; P < 0.0001), furthermore the "physiological" gradient of basoapically decreasing RS, which was reduced, but still preserved in HCM, showed a clear "inverse pattern" in patients with amyloidosis, comprising a gradual increase from base to apex. Correlation analysis of 3D speckle tracking function and CMR late gadolinium enhancement (LGE) revealed high inverse correlation of RS and LGE in CA (r =-0.82) and only mild correlation in HCM, followed by CS as second best parameter. An increasing/decreasing basoapical RS gradient yielded a sensitivity of 83% versus the CMR-derived diagnosis "CA" and "HCM." CONCLUSIONS: Three-dimensional speckle tracking echocardiography demonstrated significant differences in CA and HCM. The basoapical RS gradient displayed oppositional characteristics in CA and HCM, suggesting a "function-pattern-based" differentiation of amyloidosis and HCM.

Direct laser writing for active and passive high-Q polymer microdisks on silicon.

We report the fabrication of high-Q polymeric microdisks on silicon via direct laser writing utilizing two-photon absorption induced polymerization. The quality factors of the passive cavities are above 10(6) in the 1300 nm wavelength region. The flexible three-dimensional (3D) lithography method allows for the fabrication of different cavity thicknesses on the same substrate, useful for rapid prototyping of active and passive optical microcavities. Microdisk lasers are realized by doping the resist with dye, resulting in laser emission at visible wavelengths.

Strongly confined, low-threshold laser modes in organic semiconductor microgoblets.

We investigate lasing from high-Q, polymeric goblet-type microcavities covered by an organic semiconductor gain layer. We analyze the optical modes in the high-Q cavities using finite element simulations and present a numerical method to determine the cutoff thickness of the gain layer above which the whispering gallery modes are strongly confined in this layer. Fabricated devices show reduced lasing thresholds for increasing gain layer thicknesses, which can be explained by a higher filling factor of the optical modes in the gain layer. Furthermore, reduced lasing threshold is accompanied by a red-shift of the laser emission.

Cardiovascular magnetic resonance of myocardial infarction after blunt chest trauma: a heartbreaking soccer-shot.

Cardiac injury occasionally occurs as a result of blunt chest trauma. Most cardiac complications in chest trauma are due to myocardial contusion rather than direct damage to the coronary arteries. However, traumatic coronary injury has been reported, and a variety of underlying pathophysiological mechanisms have been proposed. We present a 26 year old patient presenting with an acute coronary syndrome as a consequence of a soccer-shot impact to the chest. CMR showed apical inferior infarction, as well as multiple small septal lesions which were presumed to have resulted from embolization. The culprit lesion was a proximal 75% LAD stenosis with a prominent plaque-rupture and thrombus-formation, and the distal LAD was occluded by thromboembolic material.

Echocardiographic assessment and monitoring of the clinical course in a patient with Tako-Tsubo cardiomyopathy by a novel 3D-speckle-tracking-strain analysis.

Using real-time 3D-speckle-tracking in the clinical course of Tako-Tsubo turned out as a quick and feasible tool for recognition and follow-up of wall motion abnormalities.

Detection of plaque rupture using 64-slice multidetector row computed tomography.

The present case report describes a 37-year-old man who presented to the emergency room with symptoms of a myocardial infarction but no high-grade stenosis on conventional catheter angiography. Consecutive multidetector row computed tomography of the coronary arteries showed an intimal flap along a fibrous plaque formation in the left anterior descending artery. This finding was found to represent a plaque rupture, and the lesion was treated with an 18 mm stent. Multidetector row computed tomography helped to correctly position the stent by identifying the exact location of the rupture along the long plaque formation.

Late enhancement using multidetector row computer tomography: a feasibility study with low dose 80 kV protocol.

AIMS: Detecting stenoses of coronary arteries with multidetector row computer tomography (MDCT) is a well feasible non-invasive method. However, there is still the problem of deciding whether a stenosis is hemodynamically relevant or not. Objective of the present study was to validate the feasibility of a low dose protocol for MDCT using 80 kV for detecting late enhancement. METHODS AND RESULTS: Using a Alderson-Rando Phantom evaluation of the effective dose of this LE protocol was performed. Ten patients (six male, four female, mean age 61) with known coronary artery disease and scheduled for a conventional coronary angiogram in our facility were subsequently recruited. All patients underwent CT-angiography (CTA) 1 day prior to magnetic resonance imaging. Five minutes after the application of 100ml contrast agent for the CTA scan, a low dose late enhancement scan (80 kV, 400 mA s maximum, ECG pulsed scan, 64 mm x 0.6mm collimation, 0.33 s tube rotation) was performed. Phantom dose measurements showed an effective dose for this protocol of 1.19 mSv (male) and 1.61 mSv (female). Fifty-six percent (5/9) of the patients showed a late enhancement on the MRI scan. Three transmural late enhancements and all four negative findings were correctly identified by CT. This represents a sensitivity of 78% (3/5), specificity of 100% (3/3), NPV of 100% (4/4) and a PPV of 97%. CONCLUSION: We were able to show that the low dose protocol is feasible and, furthermore, preliminary results look promising.

Diagnostic accuracy of multislice computed tomography for the detection of coronary artery disease in diabetic patients.

BACKGROUND: Diabetes mellitus is an important risk factor for coronary artery disease. Cardiac multislice computed tomography (MSCT) permits visualization of the coronary arteries with good sensitivity and specificity. However, at present, there are no data whether MSCT allows an accurate assessment of coronary arteries of diabetic patients, in comparison to nondiabetic patients. Thus, we compared the catheter-controlled MSCT results from diabetic and nondiabetic patients in a cohort of 116 patients with regard to sensitivity, specificity, positive predictive value, and negative predictive value, as well as image quality. METHODS AND MATERIALS: Twenty-two diabetic patients (age, 64.6+/-8.5 years; number of risk factors, 3.4+/-1.1) and 94 nondiabetic patients (age, 64.2+/-9.2 years; number of risk factors, 2.4+/-1.0) were examined by MSCT (Sensation 16 Speed 4 D, Siemens, Forchheim, Germany; gantry rotation time, 375 ms) and invasive coronary angiography. MSCT results were compared, blinded to the results of the coronary angiography with regard to the presence or absence of a significant stenosis (>50%) in a modified American Heart Association 13-segment model. Image quality was assessed on a qualitative scale between 1 (very good) and 5 (invisible) for each segment. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value were statistically not different in diabetic and nondiabetic patients (0.85/0.98/0.92/0.96 vs. 0.84/0.97/0.91/0.95). One diabetic and three nondiabetic patients had to be excluded from analysis. Diabetic patients had relevantly more risk factors (P < .05), but calcium scoring was not different in both groups (Agatston score 1090+/-1278 vs. 798+/-1033). The image quality in both cohorts was comparable. CONCLUSIONS: MSCT allows the assessment of the coronary arteries noninvasively in diabetic patients with a good sensitivity and specificity, and diabetes does not have an impact on the number of evaluable segments. Thus, MSCT is a noninvasive tool in the care of these patients.

Influence of a lipid-lowering therapy on calcified and noncalcified coronary plaques monitored by multislice detector computed tomography: results of the New Age II Pilot Study.

PURPOSE: Multislice detector computed tomography (MSCT) is an accurate noninvasive modality to detect and classify different stages of atherosclerosis. The aim of the New Age II Study was to detect coronary lesions in men without established coronary artery disease (CAD) but with a distinct cardiovascular risk profile. We also sought to assess the effect after 1 year of a lipid-lowering therapy (LLT) using 20 mg of atorvastatin. METHODS: Forty-sixe male patients (mean, 61 +/- 10 years) with an elevated risk for CAD (PROCAM score >3 quintile) without LLT were included. Native and contrast-enhanced scans were performed in all patients. A total of 27 of 46 patients received a follow-up scan (after 488 +/- 138 days). Coronary plaque burden (CPB) was assessed volumetrically. RESULTS: The prevalence of CAD was 83% (38/46 patients), and 11% (5/46) without coronary calcifications still had noncalcified plaques. Total cholesterol and low-density lipoprotein cholesterol levels decreased significantly under LLT (225 +/- 41 mg/dL vs. 162 +/- 37 mg/dL, P < 0.0001 and 148 +/- 7 mg/dL vs. 88 +/- 5 mg/dL, P < 0.001, respectively). On follow-up, calcium score and CPB remained unchanged (Agatston score: 261 +/- 301 vs. 282 +/- 360; CPB: 0.149 +/- 0.108 vs. 0.128 +/- 0.075 mL, P > 0.05), whereas mean plaque volume of noncalcified plaques decreased significantly from 0.042 +/- 0.029 mL versus 0.030 +/- 0.014 mL (P < 0.05, mean reduction 0.012 +/- 0.017 mL or 24 +/- 13%). CONCLUSIONS: Statin therapy led to a significant reduction of noncalcified plaque burden that was not reflected in calcium scoring or total plaque burden. This finding might explain the risk reduction after the initiation of statin therapy. Using multislice detector computed tomography, physicians have the potential to monitor medical treatment in patients with coronary atherosclerosis.

Coronary artery bypass grafts: assessment of graft patency and native coronary artery lesions using 16-slice MDCT.

The objective of this study was to evaluate the accuracy of electrocardiography (ECG)-gated 16-slice multidetector-row computed tomography (MDCT) in detection of stenosis of bypass grafts and native coronary arteries in patients who have undergone coronary artery bypass grafting (CABG). ECG-gated contrast-enhanced MDCT using 12 x 0.75-mm collimation was performed in 20 patients with recurrent angina 4.75 years after undergoing CABG. A total of 50 grafts, 16 arterial and 34 venous, were examined. All graft and coronary segments were evaluated for stenosis in comparison with conventional coronary angiography (CCA). Among the 80 arterial graft segments, 62 could be assessed (77.5%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 96.2%, 97.2%, 96.2%, and 97.2%, respectively. In a total of 180 venous graft segments, 167 could be assessed. Sensitivity, specificity, and positive and negative predictive values for stenosis were 98.5%, 93.9%, 91.8%, and 98.9%, respectively. MDCT could assess 179 of 260 native coronary artery segments (68.8%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 92.1%, 76.9%, 87.5%, and 84.7%, respectively. Sixteen-slice MDCT provides excellent image quality and diagnostic accuracy in detection of graft and coronary artery lesions in patients with suspected graft dysfunction.

Non-invasive evaluation of coronary artery bypass grafts using 16-row multi-slice computed tomography with 188 ms temporal resolution.

BACKGROUND: Cardiac multi-slice computed tomography (MSCT) scanners permit visualization of the coronary arteries and coronary artery bypass grafts. The latest MSCT generation with true 16-detector slices (Sensation 16 Speed 4 D, Siemens, Forchheim, Germany) provides improved temporal and spatial resolution, as well as significantly reduced scan time. To assess, whether this technical improvement has also an impact on image quality and accuracy of MSCT diagnosis in patients with previous coronary artery bypass graft (CABG) surgery the following study was conducted. METHODS AND MATERIAL: Thirteen consecutive patients (pts) (10 male, 3 female, mean age 62 +/- 6.4 [55-73] years, heart rate 68 +/- 11 [52-88] bpm) and a total number of 43 coronary bypass grafts (11 arterial, 32 venous grafts) were examined by MSCT (gantry rotation time 375 ms). In addition to the analysis of coronary bypass grafts, 13 coronary segments (sgts) were evaluated in each patient (n = 169 sgts). MSCT results were compared with coronary angiography. RESULTS: Forty-one of 43 bypass grafts (95%) were analyzable by MSCT. In conventional angiography 16 of 43 (37%) grafts were occluded. Sixteen of them were correctly diagnosed by MSCT (sensitivity 100%). One graft showed a 50% anastomosis stenosis which was also detected. Twenty-five of 27 grafts without severe lesion showed no significant stenosis in MSCT (specificity 93%, positive predictive value (PPV) 89%, negative predictive value (NPV) 100%). Ninety of 108 (83%) high-grade stenosis (>70%) of the native coronary vessels were correctly detected (sensitivity 83%, PPV 78%). From the 61 sgts without high grade stenosis 36 were correctly classified (specificity 59%, NPV 67%). If sgts number 8, 9 and 10, which are normally not target for revascularization, are excluded sensitivity rises to 89%, specificity to 71%, PPV to 87% and NPV to 75%. The correct clinical diagnosis (absence or presence of a high grade stenosis of at least one bypass graft) was achieved in all patients. CONCLUSIONS: True 16-slice MSCT with faster gantry rotation time allows detection of lesions in coronary artery bypass grafts with high sensitivity and specificity. The evaluation of native vessels in pts with known CAD remains a diagnostic challenge. However, the correct clinical diagnosis was achieved in all pts. MSCT is a non-invasive tool to assess coronary artery bypass grafts.

Technology insight: possible applications of multislice computed tomography in clinical cardiology.

With the introduction of four-slice scanners in 1999, multislice CT (MSCT) technology became available for investigative examination of the heart. Since then, MSCT technology has undergone rapid technical progress; temporal and spatial resolutions have been especially improved. The improved diagnostic image quality has led to more possible uses of MSCT being defined. At present, issues such as visualization of coronary artery bypass grafts, detection of stenoses of native coronary arteries, description of coronary anomalies, and calcium scoring, can be investigated reasonably well. Other features, such as plaque imaging and visualization of intracoronary stents, need further evaluation. A large number of factors, however, such as heart rate, atrial fibrillation, breathing artefacts and severe calcification, still influence image quality and reduce validity. In this article we provide a summary of current fields of application of cardiac MSCT. The word 'indication' is consciously avoided because official guidelines for the use of MSCT in heart examination have not yet been issued. Hopefully, prospective multicenter trials will be performed soon, providing more data with which to establish guidelines for both cardiologist and radiologist.

Image quality and diagnostic accuracy of 16-slice multidetector spiral computed tomography for the detection of coronary artery disease in elderly patients.

OBJECTIVES: To determine the image quality and diagnostic accuracy of cardiac multislice spiral computed tomography (MSCT) in elderly patients (>65 years old) in comparison to younger patients, this retrospective analysis was performed. METHODS: The catheter-controlled MSCT results from patients older than 65 years of age were compared with the results of younger patients in a cohort of 117 patients with regard to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and image quality. Fifty-three patients were older than 65 years of age (group 1: 31 men, age range: 72.2 +/- 4.1 years, number of risk factors: 2.6 +/- 1.3, Agatston score: 866 +/- 1090) and 64 were younger (group 2: 45 men, age range: 57.4 +/- 6.1 years, number of risk factors: 2.6 +/- 1.0, Agatston score: 765 +/- 1013). All patients were examined by MSCT (Sensation 16 Speed 4 D; Siemens, Forchheim, Germany, with a gantry rotation time of 375 milliseconds) and invasive coronary angiography. The MSCT results were compared blinded with the results of the coronary angiography with regard to the presence or absence of significant stenosis (>50%) in a 13-segment model. Image quality was assessed on a qualitative scale between 1 (very good) and 5 (insufficient image quality) for each segment. RESULTS: Sensitivity, specificity, PPV, and NPP were not different statistically in both groups (group 1: 0.80/0.96/0.89/0.93 and group 2: 0.89/0.98/0.93/0.97). Three patients (all <65 years old) had to be excluded from analysis because of technical problems. Image quality was significantly better in group 2. Gender, body mass index, number of risk factors, and mean heart rate were not significantly different in either group. CONCLUSIONS: Age has an impact on MSCT image quality but did not hamper diagnostic accuracy. Thus, MSCT is a noninvasive method to detect or rule out coronary artery disease independently of age. These retrospective data have to be confirmed in larger prospective trials.

Usefulness of noninvasive MSCT coronary angiography as first-line imaging technique in patients with chest pain: initial clinical experience.

PURPOSE: Comparative studies with invasive coronary angiography (ICA) indicated a good sensitivity and specificity in the noninvasive detection of coronary artery disease (CAD) using Multi-slice spiral computed tomography coronary angiography (MS-CTA). The aim was to investigate the usefulness of MS-CTA as first-line imaging technique in patients (pts) with known or suspected CAD and low to intermediate probability of a severe coronary lesion. We report on our initial clinical experience using MS-CTA without compelled ICA. MATERIAL AND METHODS: One hundred thirty six patients with chest pain underwent MS-CTA on an outpatient basis (age 60+/-10, suspicion of CAD: n=95, suspicion of restenosis: n=24, after CABG: n=17). Based on the MS-CTA results, a recommendation concerning further diagnostics and therapy was given to each pt. A telephone interview was performed after 455+/-166 days to evaluate the further clinical course. RESULTS: Per pt, 8.2+/-2.7 coronary segments could be evaluated. Based on the MSCT results, the presence of flow-limiting stenoses was excluded in n=77 (57%) pts (group I). An additional ICA was recommended in n=59 (43%) pts (group II). An ICA had been performed in meantime in 27/136 (20%) pts, and could be avoided in the majority of pts. Nevertheless, 58/136 (42%) pts reported on improved clinical symptoms and 42/136 (31%) pts of improved quality of life. CONCLUSIONS: MS-CTA was found to be useful to evaluate the need and to reduce the total number of ICA in pts with unclear chest pain. It appears to be the first noninvasive modality, which might be used on a clinical routine basis in selected groups of pts.

Coronary vessel visualization using true 16-row multi-slice computed tomography technology.

BACKGROUND: Multi-slice computed tomography (MSCT) scanners with retrospective ECG-gating permit visualization of the coronary arteries. Limited spatial and temporal resolution as well as breathing artefacts due to the scan time can cause poor distal vessel segment and side branch visualization. The latest MSCT generation with true 16-detector slices (Sensation 16), Siemens, Forchheim, Germany) provides furthermore improved temporal and spatial resolution, as well as significantly reduced scan time. To assess, whether this technical improvement has also an impact on image quality we conducted the following study. METHODS AND MATERIAL: Sixty-two consecutive patients (33 male, 29 female, mean age 63+/-8 [47-79] years, heart rate after beta-blockade 63+/-7 [45-86] bpm) with suspicion of coronary artery disease (CAD) were examined by cardiac MSCT. Parameter settings were: 0.75 mm collimation, 2.8mm table feed/rotation, caudocranial scan direction, 80 cc contrast media biphasic injection protocol, gantry rotation time 375 ms, temporal resolution 188 ms). Thirteen coronary segments (sgts) were evaluated in each patient (total number: 806 sgts). Image quality of each segment was determined as: excellent--free of motion artefacts, good--mild motion artefacts, relevant artefacts--still diagnostic value, severe calcification and insufficient image quality--not visualized segment. RESULTS: 301/806 (37%) sgts showed excellent and 294/806 (36%) sgts good image quality. Relevant artefacts were seen in 107/806 (13%) sgts, calcifications in 41/806 (5%) sgts. 63/806 (8%) sgts could not be visualized (34 of them (54%) either segment 9 or 10). Diagnostic image quality was achieved in 702/806 (87%) sgts. CONCLUSIONS: Due to true 16-slice technology and faster gantry rotation time MSCT image quality could be improved and allows a visualization of the entire coronary tree. Larger, randomized, catheter-controlled studies have to be conducted to determine, whether this improved visualization also translates into better diagnostic accuracy.