Fibroblast Activation Protein Inhibitor-Positron Emission Tomography in Aortitis: Fibroblast pathology in active inflammation and remission.

OBJECTIVES: Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. METHODS: 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. RESULTS: Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found.In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. CONCLUSIONS: This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.

Whole-body biodistribution of the cannabinoid type 1 receptor ligand [18F]MK-9470 in the rat.

The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [18F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %ID/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland-Altman plots were computed. The highest uptake of [18F]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [18F]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90min acquisition protocols. High hepatic accumulation and metabolism of [18F]MK-9470 occur with mainly enteral excretion, which may vary considerably over time - a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [18F]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals.

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

Δ9-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [18F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of < 1 ng/ml (injected dose: ≤ 0.01 mg/kg) corresponded to an increased glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies.

Primary non-refluxive megaureter in children: single-center experience and follow-up of 212 patients.

PURPOSE: Primary non-refluxing megaureter (pMU) is a multifaceted and challenging congenital pathology of the urinary tract. We report our 23-year experience with this anomaly in terms of presentation, diagnostic work-up and management. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 212 children diagnosed with pMU between 1986 and 2009 at our institution. Mean follow-up was 45.17 (0-192) months. RESULTS: Of the total, 168 (79 %) children presented with upper urinary tract dilation on perinatal ultrasound screening. In 44 (21 %) patients, the diagnosis was made following diagnostic work-up of a urinary tract infection (UTI, 18 %) or flank pain (3 %). In total, 203 of 254 pMUs (79.9 %) were successfully treated conservatively during the 23-year observation period. Forty-eight children (23 %) underwent ureteric reimplantation. UTIs occurred in 91 of 212 children (43 %). Of these, 41 (45 %) occurred despite antibacterial infection prophylaxis. Within the past three decades, there has been a marked shift from surgical toward conservative therapy at our institution. CONCLUSION: Neonatal renal ultrasound is the method of choice to timely identify children with pMU and, alongside dynamic renography, to monitor the clinical course. Nowadays, only a minor subset of children with asymptomatic course requires surgical correction. Antibacterial prophylaxis has the potential to reduce the risk of febrile UTIs. Prospective randomized studies are warranted to provide evidence of the beneficial effect of antibacterial prophylaxis.

Haematopoietic toxicity of radium-223 in patients with high skeletal tumour burden.

UNLABELLED: In patients with metastasized, castration resistant prostate cancer (mCRPC) treatment with radium-223 (Xofigo) is an attractive therapeutic option. In particular, patients with high tumour load seem to profit from this treatment in regard of survival and quality of live. Aim of this study was to stratify mCRPC patients according to a quantitative imaging marker derived from routine bone scans (EXINI bone) and analyze haematopoietic toxicity of Xofigo in these patients. PATIENTS, METHODS: Toxicity and oncologic outcome were investigated in a cohort of 14 patients with high tumour load. Additionally, based on a web survey, experience of toxicity in 41 high tumour load patients in Germany in 2014 was collected. RESULTS: In patients with a bone scan index (BSI) greater than 5, significant toxicity occurred in more patients than expected from the ALSYMPCA trial. This was associated with application of fewer cycles. Similar experiences have been made in other centers in Germany. Approximately 7% of these patients will need very long time or will not recover from grade ≥ 3 toxicity. CONCLUSION: Close follow-up of haematopoietic indices and, in case of toxicity, early termination of therapy is in particular necessary in late stage disease where limited bone marrow reserve is likely.

[Perfusion brain imaging with SPECT-technique. German Guideline S1]. / Hirnperfusions-SPECT mit 99mTc-Radiopharmaka. DGN-Handlungsempfehlung (S1-Leitlinie).

This paper describes the guideline for perfusion brain imaging with SPECT-technique published by the Association of the Scientific Medical Societies in Germany (AWMF).The purpose of this guideline is to provide practical assistance for indication, examination procedures, findings and their interpretation also reflecting the present state of the art. Information and instruction are given regarding indication, preparation of the patients and examination procedures of brain perfusion SPECT, including preparation and quality control of the tracer as well as the radiation dosimetry, technical performance of image acquisition with the gamma-camera and image processing. Also advices for interpretation of findings are given. In addition, possible pitfalls are described.

Evaluation of cannabinoid type 1 receptor expression in the rat brain using [¹8F]MK-9470 microPET.

PURPOSE: The ligand [(18)F]MK-9470 is an inverse agonist binding with high affinity and specificity to the cannabinoid type 1 (CB1) receptor. In this study, a semiquantitative acquisition and analysis protocol for investigation of the CB1 receptor distribution in the rat brain was established. METHODS: Two C57BL/6N mice (one CB1 (-/-) and one wild-type) and 19 Sprague Dawley rats were investigated using a Focus 120 microPET scanner. Seven rats were scanned twice for test-retest evaluation, six rats were scanned for blocking experiments using the inverse CB1 receptor agonist rimonabant, and 19 rats were scanned for baseline studies. Percentage injected dose per millilitre (%ID/ml) or uptake ratios (VOItarget/VOIwhole brain) were calculated. A Bland-Altman-plot was computed and mean values were compared using a two-sided paired t test. RESULTS: Comparing the data from the CB1 (-/-) mouse and the wild-type mouse, [(18)F]MK-9470 showed good specificity. Regarding the rat data, there was no relationship between the difference between the test and retest measurements or their mean value. The test and retest data showed a strong correlation (ρ c = 0.846, p ≤ 0.01; r Pearson = 0.857). Equivalence was not found for all regions and not even in the pons at baseline or under blocking condition. Only the baseline studies showed the highest levels of uptake in the caudate-putamen and thalamus, whereas moderate uptake was found in the hippocampus, hypothalamus and cerebellum, and the lowest uptake was observed in the cortex, amygdala and pons. CONCLUSION: A reference region is not available; however, the proposed analysis method using the parameter uptake ratio is simple and delivers stable results allowing the discrimination of distinct brain regions.

PET lung ventilation/perfusion imaging using (68)Ga aerosol (Galligas) and (68)Ga-labeled macroaggregated albumin.

Pulmonary imaging using ventilation/perfusion (V/P) single-photon emission tomography (V/P scan) with Tc-99m-labeled radiotracers is a well-established diagnostic tool for clinically suspected pulmonary embolism (PE). Ga-68 aerosol (Galligas) and Ga-68-labeled macroaggregated albumin (MAA) are potential tracers for positron emission tomography (PET) lung V/P imaging and could display an advantage over conventional V/P scans in terms of sensitivity and specificity. After radiochemical and animal studies, the clinical applicability of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was investigated in an exploratory study in patients with clinical suspicion of PE. PET scans were acquired using a 16-slice Gemini TF positron emission tomography/computed tomography (PET/CT) scanner. The acquisition protocol included low-dose computed tomography (CT) for attenuation correction (AC). Dosimetry calculations and continuative phantom measurements were performed. Structural analyses showed no modification of the particles due to the labeling process. In addition, in vitro experiments showed stability of Ga-68 MAA in various media. As expected, Ga-68-labeled human serum albumin microspheres (HSAM) were completely retained in the lung of the animals. In clinical use, PET lung ventilation and perfusion imaging using Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was successful in all cases. In one case a clinically suspected PE could be detected and verified. The administered activity of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA may be reduced by more than 50%, resulting in comparable radiation exposure to conventional V/P scans. In conclusion, Ga-68 aerosol (Galligas) and Ga-68-labeled MAA are efficient substitutes for clinical use and could be an interesting alternative with high accuracy for lung V/P imaging with Tc-99m-labeled radiotracers, especially in times of Mo-99 shortages and increasing use and spread of PET/CT scanners and Ga-68 generators, respectively.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

Estimation of further disease progression of Parkinson's disease by dopamin transporter scan vs clinical rating.

BACKGROUND: Imaging techniques like ß-CIT Scan are valuable diagnostic tools for Parkinson's disease (PD) and correlate in most cases with clinical symptoms. In some patients, however, clinical and imaging data are conflicting. It has not yet been evaluated, which parameter provide more information about severity and disease progression in those patients. AIM: To estimate the predictive value of UPDRS and ß-CIT in PD on clinical impairment at follow up. DESIGN AND METHODS: In a longitudinal study, 44 PD patients who underwent ß-CIT Scan for diagnostic purpose were followed up for a mean of 44 months. At baseline we assessed UPDRS motor score as well as the subtype of PD, presence of dementia or motor complications. Disease staging at follow up was displayed by UPDRS II (ADL) and III (motor score) as well as by Hoehn & Yahr classification. RESULTS: ß-CIT could significantly discriminate PD patients from controls and the tracer uptake ratios (UR) correlated well with UPDRS motor score at baseline. There was, however, only a weak correlation between UR and staging parameters at follow up, whereas UPDRS at baseline was highly correlated with impairment at follow up. CONCLUSION: The data suggest a more significant predictive value of UPDRS motor score on disability in the course of disease progression than ß-CIT Scan. Low receptor binding may not be mistaken for a bad prognosis.

Central opioidergic neurotransmission in complex regional pain syndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is a chronic pain condition characterized by sensory, motor, and autonomic symptoms. It develops after limb trauma and may be associated with relevant psychiatric comorbidity. As there is evidence for central pathophysiology which might be related to an altered opioidergic neurotransmission, we investigated the cerebral opioid receptor status under resting conditions in this patient population. METHODS: In this case-control study, 10 patients with CRPS and 10 age- and gender-matched healthy subjects underwent a PET scan using the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine. As a surrogate for regional cerebral opioid receptor availability, the opioid receptor binding potential (OR-BP) was assessed by means of the modified Logan plot with reference region input for categorical group comparison and correlation with clinical data in the patient group. RESULTS: Patients with CRPS showed reduced OR-BP in contralateral amygdala and parahippocampal gyri and increased OR-BP in contralateral prefrontal cortical areas. When OR-BP in the midcingulate cortex and the ipsilateral temporal cortex was low, the McGill pain rating index was high. In general, when anxiety and depression scales were high, contralateral temporal OR-BP was high as well. In addition, the anxiety scale decreased with increasing OR-BP in the contralateral parahippocampal cortex. CONCLUSIONS: These results demonstrate altered central opioidergic neurotransmission in CRPS. The correlation of regional opioid receptor availability to measures of pain, anxiety, and depression underlines the clinical importance of these findings.

Cortical control of thermoregulatory sympathetic activation.

Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32 degrees C), temperature was either decreased to 7 degrees C (cold), increased to 50 degrees C (warm) or kept constant (32 degrees C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke.

6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression.

CONTEXT: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. OBJECTIVE: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. DESIGN AND SETTING: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. PATIENTS: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex, subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein, two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive adrenal incidentalomas. MAIN OUTCOME MEASURES: In all patients computed tomography scan and/or magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed. Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine transporter (VMAT)-1 and -2 and other markers. RESULTS: A total of 64 lesions were found with both functional imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1 expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause. CONCLUSION: FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-scintigraphy.

In vivo molecular imaging of somatostatin receptors in pancreatic islet cells and neuroendocrine tumors by miniaturized confocal laser-scanning fluorescence microscopy.

The aim of the study was to evaluate real time in vivo molecular imaging of somatostatin receptors (sstrs) using a handheld miniaturized confocal laser scan microscope (CLM) in conjunction with fluorescein-labeled octreotate (OcF) in healthy mice and murine models of neuroendocrine tumors. For CLM a small rigid probe (diameter 7 mm) with an integrated single line laser (488 nm) was used (optical slice thickness 7 mum; lateral resolution 0.7 mum). OcF was synthesized via Fmoc solid-phase peptide synthesis and purified by HPLC showing high-affinity binding to the sstr2 (IC(50) 6.2 nmol). For in vitro evaluation, rat and human pancreatic cancer cells were used and characterized with respect to its sstr subtype expression and functional properties. For in vivo confocal imaging, healthy mouse pancreatic islet and renal tubular cells as well as immunoincompetent nude mice harboring sstr-expressing tumors were evaluated. Incubation of sstr-positive cells with OcF showed a specific time- and dose-dependent staining of sstr-positive cells. CLM showed rapid internalization and homogenous cytoplasmatic distribution. After systemic application to mice (n = 8), specific time-dependent internalization and cytoplasmatic distribution into pancreatic islet cells and tubular cells of the renal cortex was recorded. After injection in tumor-harboring nude mice (n = 8), sstr-positive cells selectively displayed a cell surface and cytoplasmatic staining. CLM-targeted biopsies detected sstr-positive tumor cells with a sensitivity of 87.5% and a specificity of 100% as correlated with ex vivo immunohistochemistry. CLM with OcF permits real-time molecular, functional, and morphological imaging of sstr-expressing cell structures, allowing the specific visualization of pancreatic islet cells and neuroendocrine tumors in vivo.

Advocating neuroimaging studies of transmitter release in human physical exercise challenges studies.

This perspective attempts to outline the emerging role of positron emission tomography (PET) ligand activation studies in human exercise research. By focusing on the endorphinergic system and its acclaimed role for exercise-induced antinociception and mood enhancement, we like to emphasize the unique potential of ligand PET applied to human athletes for uncovering the neurochemistry of exercise-induced psychophysiological phenomena. Compared with conventional approaches, in particular quantification of plasma beta-endorphin levels under exercise challenges, which are reviewed in this article, studying opioidergic effects directly in the central nervous system (CNS) with PET and relating opioidergic binding changes to neuropsychological assessments, provides a more refined and promising experimental strategy. Although a vast literature dating back to the 1980s of the last century has been able to reproducibly demonstrate peripheral increases of beta-endorphin levels after various exercise challenges, so far, these studies have failed to establish robust links between peripheral beta-endorphin levels and centrally mediated behavioral effects, ie, modulation of mood and/or pain perception. As the quantitative relation between endorphins in the peripheral blood and the CNS remains unknown, the question arises, to what extent conventional blood-based methods can inform researchers about central neurotransmitter effects. As previous studies using receptor blocking approaches have also revealed equivocal results regarding exercise effects on pain and mood processing, it is expected that PET and other functional neuroimaging applications in athletes may in future help uncover some of the hitherto unknown links between neurotransmission and psychophysiological effects related to physical exercise.

Visual-motion suppression in congenital pendular nystagmus.

Patients with a congenital pendular nystagmus are known not to experience oscillopsia in a normal visual environment. The data of a 31-year-old female patient suffering from a congenital pendular nystagmus are presented. The aim of the fluorodeoxyglucose positron emission tomography (FDG-PET) experiment was to analyze the regional cerebral glucose metabolism (rCGM) during minimal as well as maximal nystagmus. Video-oculography showed a maximum in frequency of the horizontal pendular nystagmus during gaze to the left, whereas the zone of minimal nystagmus was 10 degrees to the right. Two sessions with an 18F-fluorodeoxyglucose tracer were performed to analyze cerebral blood-glucose utilization when fixating an object in the areas of maximal and of minimal nystagmus. A structural MRI in a clinical 1.5-T scanner was acquired to superimpose the PET results onto the unique anatomy of the patient. By statistical analysis a significant increase in the rCGM in the cerebellar nodulus and a relative decrease in the area of MT/V5 bilaterally during maximal nystagmus were found. When the patient was looking in her null zone, rCGM was increased in V1 and MT/V5 bilaterally. To the best of the authors' knowledge, this is the first proof by means of functional imaging of a suppression of oscillopsia in higher-order visual cortex areas in a patient with a congenital nystagmus.

Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET.

Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN-) by a magnetic resonance imaging method (MRI; T2 relaxation times) known to reveal tissue inhomogeneity following abnormal iron content and by F-Dopa PET to assess nigrostriatal function.

Laparoscopic radioisotope-guided sentinel lymph node mapping and excision of the rectum--an experimental study.

BACKGROUND: Patients with a low-risk T1 rectal carcinoma can undergo the therapy of a local excision. In these patients the lymph node (LN) status remains unknown. There is a potential risk of up to 7% for nodal metastasis. To investigate the possibility of using the sentinel lymph node (SLN) concept, an experimental study on pigs was undertaken. The objective was to laparoscopically identify and extract SLNs from the rectum using a radioisotope (RI). METHODS: The experiment was conducted in 30 pigs, since the sample size calculation indicated that with 30 animals a two-sided 95% confidence interval for a single proportion using the large sample normal approximation would extend at most 0.107 from the observed proportion of 0.9. One milliliter of a mixture of the RI Technetium 99 m (Tc99 m) and patent blue V dye was administered in the rectum endoscopically and after the lapse of 1 h, we laparoscopically identified and excised all SLNs using a laparoscopic gamma camera probe. RESULTS: We found in all operated pigs (n = 30) at least one SLN (lymph node with highest measured counts per second (cps)). In mean we detected 1.6 SLN (range one to three SLNs). In 28 cases, the SLN concept was successful. Sensitivity for detecting SLNs was 93% (n = 28/30), the probe count rate ranged from 600-10,000 cps with a median of 3,800. CONCLUSION: Minimal invasive mapping and excision of SLN of the rectum using a RI is feasible. The sensitivity for detecting SLN was high (93%). The application of this procedure on humans seems to be possible.