Indocyanine green-enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging.

OBJECTIVE: Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months). METHODS: FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease (1,380 joints). RESULTS: With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial (κ = 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2. CONCLUSION: Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials.

Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology.

BACKGROUND: Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis. METHODS: 252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands. RESULTS: In an FOI sequence, three phases could be distinguished (P1-P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls. CONCLUSION: ICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.

Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions.

Fluorescence imaging using the dye indocyanine green as a contrast agent was investigated in a prospective clinical study for the detection of rheumatoid arthritis. Normalized variances of correlated time series of fluorescence intensities describing the bolus kinetics of the contrast agent in certain regions of interest were analyzed to differentiate healthy from inflamed finger joints. These values are determined using a robust, parameter-free algorithm. We found that the normalized variance of correlation functions improves the differentiation between healthy joints of volunteers and joints with rheumatoid arthritis of patients by about 10% compared to, e.g., ratios of areas under the curves of raw data.

Near-infrared imaging of the breast using omocianine as a fluorescent dye: results of a placebo-controlled, clinical, multicenter trial.

OBJECTIVES: To evaluate the efficacy of the near-infrared (NIR) dye Omocianine in a placebo-controlled, dose-escalating multicenter trial for the detection of malignant breast lesions by using a NIR imaging system. MATERIALS AND METHODS: The study was approved by the ethical review board of Berlin and Münster,, and all participants provided written informed consent. Fifty-two consecutive patients were examined with NIR imaging before, during, and after intravenous injection of Omocianine. Three-dimensional absorption and fluorescence diffuse optical tomography scans were recorded simultaneously on a prototype NIR imaging unit (Computed Tomography Laser Mammography, Imaging Diagnostic Systems, Inc., Ft. Lauderdale, FL). Two readers assessed the images in consensus and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence diffuse optical tomography mammograms. Imaging results were compared with histopathologic findings. To analyze whether lesion detection rate for malignant lesions depended on the size of the lesion, lesions were dichotomized into those measuring less than 20 mm and those measuring 20 mm or more. Moreover, the shortest diameter between the center of the target lesions and the skin was measured on axial optical mammography data. RESULTS: There were a total of 53 target lesions. Histopathologically, 22 target lesions were diagnosed as benign and 31 target lesions as malignant. In the absorption mode, a detection rate of 11.8% for benign and 44.4% for malignant lesions across all dose groups was found. In the fluorescence mode, a detection rate of 17.6% was revealed for benign and 55.6% for malignant lesions across all dose groups. For dose group 0.1 mg/kg, a detection rate of 100% was found for malignant lesions in the fluorescence mode and 71.4% in the absorption mode. Across all dose groups in the fluorescence mode, detection rate for malignant target lesions in breasts smaller than the median axial breast diameter of 12.8 cm was higher with 69.2% than in median diameters ≥ 12.8 cm with 46.2%. Omocianine-enhanced fluorescence optical mammography allowed a better detection of more superficially located lesions, with detection rates for a lesion-skin distance <20 mm of 63.6%, for <30 mm of 47.4% and for ≥ 30 mm of 25%. Malignant target lesions with a diameter ≥ 20 mm were slightly better detected with 61.5% in contrast to suspicious lesions <20 mm with 53.8%. Optimal imaging time points varied strongly among the different target lesions and Omocianine dose groups, with a mean optimal time point for malignant lesions at 188 ± 385 minutes. CONCLUSION: Preliminary data suggest that fluorescence imaging after Omocianine administration has the potential to detect malignant breast lesions. As our study showed considerable variations in the detection of breast cancer at different fluorophore concentrations ranging from 20% to 100%, future work needs to be done to assess the suitable dose for NIR imaging.

Comparison of two tricarbocyanine-based dyes for fluorescence optical imaging.

Optical technologies are evolving in many biomedical areas including the biomedical imaging disciplines. Regarding the absorption properties of physiological molecules in living tissue, the optical window ranging from 700 to 900 nm allows to use fluorescent dyes for novel diagnostic solutions. Here we investigate the potential of two different carbocyanine-based dyes fluorescent in the near infrared as contrast agents for in vivo imaging of subcutaneously grown tumours in laboratory animals. The primary aim was to modify the physicochemical properties of the previously synthesized dye SIDAG to investigate the effect on the in vivo imaging properties.

Improved vascular opacification in cerebral computed tomography angiography with 80 kVp.

PURPOSE: We sought to intraindividually compare computed tomography angiographies (CTAs) acquired at 80 kVp and 120 kVp with respect to vessel contrast, noise level, and radiation dose. MATERIAL AND METHODS: CTA was performed on a single-slice CT scanner using tube voltages of 80 kVp and 120 kVp in 29 patients with arteriovenous malformations. Mean Hounsfield Units (HU) were evaluated for different vessels and brain parenchyma. To determine contrast-to-noise ratios (CNRs), noise levels were estimated from phantom measurements. RESULTS: The calculated effective dose to male/female patients was 0.4/0.5 mSv for 80 kVp and 0.7/0.8 mSv for 120 kVp. CT density in blood vessels was between 297 and 458 HU for 80 kVp and 152 and 229 HU for 120 kVp (P<0.0001). Despite an increased noise level in the low-voltage images, the CNR was 26-59% higher at 80 kVp than at 120 kVp (P<0.05). CONCLUSION: The use of a reduced tube potential leads to improved CNR in CTA of the cerebral vasculature and a markedly reduced radiation exposure to patients.

Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors.

PURPOSE: To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS: A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS: Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION: A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

Ventricular oversensing: a study of 101 patients implanted with dual chamber defibrillators and two different lead systems.

UNLABELLED: Modern dual chamber ICD systems are able to overcome various sensing problems. However, improvement of their performance is still required. The aim of this study was to assess the sensing function in 101 consecutive patients (84 men, 17 women; mean age 63 +/- 12 years; mean follow-up 24 +/- 4 months) implanted with dual chamber defibrillators and integrated (IB) or dedicated bipolar (DB) lead systems. Follow-up data were analyzed for the presence of ventricular oversensing. Oversensing occurred in 25 (25%) patients, significantly more frequent in patients implanted with IB compared to DB lead systems (21/52 vs 4/49, P = 0.0002). Patients with cardiomyopathies (CMs) were more prone to sensing malfunctions than patients with no CM (12/30 vs 13/71, P = 0.04). T wave oversensing (n = 14), respirophasic ventricular oversensing (n = 4), and P wave oversensing (n = 6) were the most common pitfalls of ventricular sensing. P wave oversensing was unique to the IB lead system. CT scans performed in these patients disclosed the position of the RV coil to be proximal to the tricuspid area. Four patients received inappropriate ICD shocks due to oversensing. In all but two patients who received lead revision, oversensing was resolved by noninvasive means. IN CONCLUSION: (1) ventricular oversensing is a common problem occurring in up to 25% of patients with dual chamber ICDs; (2) P wave oversensing is a ventricular sensing problem affecting function of 11% of dual chamber devices with IB lead systems; (3) IB leads are significantly more susceptible to T wave and P wave oversensing than DB leads; and (4) patients with cardiomyopathies are more prone to oversensing than patients with other heart diseases.

Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure.

BACKGROUND: Cardiovascular mortality is excessive in young adults with end-stage renal disease (ESRD). The factors contributing to ESRD-related vascular disease are incompletely understood. Young adults with childhood-onset chronic renal failure (CRF) are uniquely suited for risk factor assessment because of their long-term exposure at an age when vascular pathology in the general population is still minimal. METHODS AND RESULTS: We used novel noninvasive technologies to screen for coronary and carotid artery disease in 39 patients with ESRD aged 19 to 39 years with childhood-onset CRF presently treated by dialysis or renal transplantation. Coronary artery calcification burden was assessed by CT scan with ECG gating and the intima-media thickness (IMT) of the carotid arteries by high-resolution ultrasound. Coronary artery calcifications were present in 92% of patients; calcium scores exceeded the 95th age- and sex-specific percentiles >10-fold on average. Carotid IMT was significantly increased compared with matched control subjects. Both coronary calcium scores and IMT were associated with cumulative dialysis and ESRD time and the cumulative serum calcium-phosphate product. Coronary calcium scores were strongly correlated with C-reactive protein and Chlamydia pneumoniae seropositivity, time-averaged mean serum parathyroid hormone, and plasma homocysteine. C-reactive protein and parathyroid hormone independently predicted coronary calcium accumulation. Smoking, obesity, and HbA1c were correlated with IMT in the control subjects but not in the patients. CONCLUSIONS: Young adults with childhood-onset CRF have a high prevalence of arteriopathy associated with indicators of microinflammation, hyperparathyroidism, calcium-phosphate overload, and hyperhomocysteinemia but not traditional atherogenic risk factors. These risk factors persist even after successful renal transplantation.