Conversion from mild cognitive impairment to dementia: influence of folic acid and vitamin B12 use in the VITA cohort.

OBJECTIVE: Increased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia. PARTICIPANTS: A community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI. DESIGN: Prospective study with a retrospective evaluation of vitamin intake. MEASUREMENTS: Laboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up. RESULTS: The self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users. CONCLUSIONS: These results from a middle European study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.

[Nuclear medicine in Europe: education]. / Nuklearmedizin in Europa. Die Ausbildungssituation.

The technical developments that have taken place in the preceding years (PET, hybrid imaging) have changed nuclear medicine. The future cooperation with radiologists will be challenging as well as positioning nuclear medicine in an European context. It can also be expected that education in nuclear medicine will undergo a harmonization process in the states of the European Union. In this paper, we describe how nuclear medicine education is organized in several European countries. We aim to stimulate constructive discussions on the future development of the specialization in nuclear medicine in Germany.

[Diagnostic reference value. Critical evaluation of the term with the example of nuclear medicine studies in Austria]. / Diagnostischer Referenzwert. Kritische Wertung des Begriffes am Beispiel nuklearmedizinischer Untersuchungen in Österreich.

UNLABELLED: The aim of this study was to collect administered activities of important nuclear medicine diagnostic examinations and to identify frequencies as well as age distributions in the light of hybrid devices in Austria. Based on the survey data a re-evaluation of dose reference levels for nuclear medicine has been published in June 2010 in the novella of the Austrian Medical Radiation Protection Regulation (MedStrSchV) (8), also an estimate of the average individual doses of the total population. Accurate data on nuclear medicine studies of 34% of all Austrian nuclear medicine units could be collected. RESULTS: Extrapolated there are about 150000 nuclear medicine examinations per year performed in Austria. The median age of patients is thereby 62 years. The results of this study resulted in 65% of the dose reference values to change, whereas 48% had to be revised downwards and 17% upwards. Additionally, 5 new reference values were included in the list; three more were taken out, however. The estimation of the individual effective patient dose for each offered examination was on average 4.7 mSv. An extrapolation based on the total exposure of the population with regard to uninvolved persons and children led to 0.07 mSv per year by nuclear medicine examinations. CONCLUSION: The published diagnostic reference values correspond to the normal investigative practice in Austria and are compliant with most international recommendations. The term "optimal value" has been removed from the text of the law, because such wording would be misleading.

Medical preparedness in radiation accidents: a matter of logistics and communication not treatment!

The currently reactor wreckage in Fukushima raised the following important questions: Is our knowledge of the possible dangers of ionizing radiation sufficient to warrant special action? What is the role of the medical community in technical radiation accidents from Windscale to Fukushima? What is the role of the medical community in terrorist radiation attacks? Are we prepared for those challenges? How can medical services communicate information in the media framework? What have we learned recently? And, what should be improved? In this review of the current literature on ionizing radiation, we try to answer these questions. Our conclusion is that medical services have to improve their communication skills and convince the public that the dangers of ionizing radiation can be quantitated within certain limits to support a qualified discussion about its risks and benefits.

Tumor growth of suspected meningiomas in clinically healthy 80-year-olds: a follow up five years later.

BACKGROUND: The incidence of clinically silent meningiomas in 75-year-old individuals was determined five years ago in the Vienna Transdanube Ageing Study (VITA). At the time a watch-and-wait approach was recommended in cases of incidentally discovered meningiomas. METHODS: 420 out of the initial cohort of 532 test persons underwent control investigations after 2.5 and 5 years. Six of the nine known tumors were measured again and the patients underwent clinical, neurological and psychological tests. Changes in tumor size were determined and all new tumors seen on MRI investigation were carefully reviewed. RESULTS: Tumor growth was minimal in all six cases that were followed over the entire period. Two of the original meningioma patients had died and one patient had undergone tumor resection. CONCLUSIONS: The watch-and-wait approach recommended after the VITA study was confirmed by the present investigation. Tumor growth was slow in all cases; no clinical symptoms have been registered thus far. The intervals between control investigations may even be prolonged depending on the location of the tumor. In this age group the operation appears to pose a greater risk than the presence of an asymptomatic tumor.

Validity of sentinel lymph node (SLN) detection following adjuvant radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC).

The effect of preoperative radio chemotherapy on lymphatic drainage and intraoperative gamma probe-guided sentinel lymph node detection has yet not been investigated. In this study, we study 13 patients with SCC. Sentinel lymph node (SLN) imaging of the patients was performed using SPECT-CT. Special care was taken to use identical injection sites for both studies. Imaging comprised planar and SPECT, iterative reconstruction and were viewed with the co-registered CT image. The results were validated by comparison with the histological results of intraoperative gamma probe detection and histology of the completed neck dissection. Identical SLNs were found in 6/13 patients. In 2/13 cases SLN biopsies were false-negative. In 4/13 patients preoperative SLN imaging identified more/additional nodes than the initial imaging, whereas fewer nodes were seen in 3/13 patients. Neither the primary tumor site nor the TNM stage was predictive for changes in the lymphatic drainage pattern. No constant effect of irradiation could be demonstrated. Preoperative radio chemotherapy has an unpredictable influence on the lymphatic drainage pattern in HNSCC. Consequently, the intraoperative gamma probe-guided sentinel lymph node detection after radio chemotherapy does not reveal the SLN of carcinogenesis. Thus, we advise fused functional/anatomical imaging (SPECT-CT) before and after radiochemotherapy if the SLN concept is utilized in HNSCC.

Spontaneous osteonecrosis of the knee: biochemical markers of bone turnover and pathohistology.

OBJECTIVE: The aim of this study was to evaluate bone metabolism in patients with spontaneous osteonecrosis (ON) of the medial femoral condyle. METHOD: In 22 consecutive patients, undergoing total knee arthroplasty, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. Specimens of the medial femoral condyle were available for histologic examination and the lesion size, assessed on radiographs, was compared with the results from bone turnover measurements. Twenty patients with osteoarthritis (OA) of the knee served as a control. Bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. RESULTS: Mean serum levels of analytes were not different in patients with ON and OA. The serum concentrations averaged 16.2 vs 13.3 ng/mL (OC), 10.2 vs 12.1 ng/mL (bone ALP), 4.6 vs 4.1 ng/mL (ICTP), and 33.2 vs 40.4 ng/mL (PINP) in patients with ON and OA, respectively. In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly when compared to serum levels. The mean marker concentrations in samples obtained from cancellous bone were 33.8 vs 43.3 ng/mL (OC), 34.6 vs 37.3 ng/mL (bone ALP), 64.8 vs 36.1 ng/mL (ICTP, P=0.02), and 208.0 vs 176.2 ng/mL (PINP) in patients with ON and OA, respectively. The lesion size was at mean 440.5+/-275.8mm(2) in knees with ON and did not correlate with either serum or bone concentrations of all markers tested (P>0.1). CONCLUSION: The marked elevation of markers in samples obtained from cancellous bone pointed at increased turnover in both diseases when compared to healthy individuals. In line with histologic findings of necrosis of subchondral bone, focal degradation of collagen type I was more pronounced in knees with ON. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis spontaneous ON.

The importance of delayed images in gastrointestinal bleeding scintigraphy.

Although radionuclide methods for the detection of gastrointestinal (GI) bleeding have been available for more than 20 years, the value of delayed images in GI bleeding scintigraphy is still regarded controversially. The aim of this study was to determine the value of delayed images in a group of patients with predominantly low-grade intermittent bleeding. Eighty-nine consecutive GI bleeding scintigraphies of 75 patients were analysed retrospectively. All patients were referred to our department after other diagnostic methods had failed to identify the localization of GI bleeding. After the dynamic study, delayed images were acquired for up to 24 h until a bleeding site was identified. Data on the clinical outcome were available in all but five patients. No patient with a negative scan died from GI bleeding. A positive result was found in 41 patients (55%). The scans of 11 of these 41 patients (27%) became positive during dynamic imaging. Four required immediate surgery and, in another patient, surgery was not performed because of diffuse bleeding of the entire GI tract. One patient died without surgical intervention. Thirty-three scans of 30 of these 41 patients (73%) were positive on delayed imaging only, leading to surgery in 12 individuals. Our findings demonstrate the importance of delayed images in GI bleeding scintigraphy. Many of our patients who required surgery had scans that did not become positive for several hours.

Effects of irradiation on 99m Tc sestamibi and 201Tl uptake in a human papillary thyroid carcinoma cell line.

Both 99mTc sestamibi and 201Tl have been used in conjunction with 131I scintigraphy for follow-up of patients with thyroid cancer. The aim of the study was to determine if irradiation affects tracer uptake in papillary thyroid cancer cells. The human papillary carcinoma cell line (PAP/ES-1) used in this study was generated from a papillary thyroid tumour obtained after surgery. For the in vitro uptake studies cells were seeded at 2 x 105 cells/well into 12-well microtitre plates. Irradiation was performed with a 60Co source (total dose, 2 Gy and 10 Gy). After incubation at 37 degrees C the supernatants were saved for determination of the unincorporated activity. The reaction was stopped by washing the cells four times in ice cold phosphate buffered saline. Total cellular uptake was determined by measuring cell lysate radioactivity in a Compugammasystem and was expressed as per cent uptake per mg of total cellular protein. At continuous incubation 201Tl uptake was significantly (P<0.01) higher after radiation whereas no effect of irradiation was found on 99mTc sestamibi uptake. Pulsed experiments revealed that irradiated cells displayed a faster 201Tl efflux. The net tracer retention at 90 min was similar to 201Tl to that of 99mTc sestamibi. We conclude that 99mTc sestamibi kinetics in thyroid cancer are not affected by irradiation and may therefore be superior to 201Tl in the follow-up of thyroid cancer shortly after radiotherapy.

Does motion analysis in postexercise gated sestamibi SPECT reflect rest left ventricular motion even in severe coronary artery disease?

PURPOSE: Evidence has suggested that postexercise gated Tc-99m sestamibi SPECT (GSPECT) provides combined information about resting wall motion and exercise perfusion. No data have been published about possible differences in wall motion analysis between postexercise and resting GSPECT. METHODS: Fifty patients underwent postexercise (symptom-limited bicycle stress) and rest GSPECT and cardiac catheterization with contrast ventriculography. In 35 patients, additional rest planar Tc-99m RBC radionuclide ventriculography (RNV) was performed. Four observers independently performed left ventricular ejection fraction (LVEF) calculations and visual analysis of regional wall motion (graded in four stages) for all studies. RESULTS: The LVEF calculations in GSPECT revealed a statistically significant difference between postexercise (45.8 +/- 15.7%) and rest (48.0 +/- 16.1%; P < 0.05) determination. Postrest GSPECT LVEF showed a better correlation with LVEF determination performed with contrast ventriculography and RNV than did postexercise GSPECT LVEF. The reduced postexercise wall motion could be shown in segments with exercise-induced ischemia and in those with normal regional perfusion but not in segments with irreversibly abnormal perfusion. CONCLUSIONS: Postexercise GSPECT provides reliable information regarding global wall motion even in severe coronary artery disease, but regional wall motion is underestimated compared with rest GSPECT, because of an imprecise surface detection algorithm in ischemic wall segments and possibly postexercise stunning in severe coronary artery disease.

Splenosis mimicking tumor recurrence in renal cell carcinoma: detection on selective spleen scintigraphy.

A 2-year-old boy had been operated on for a giant renal cell carcinoma including splenectomy because of disrupture of the splenic capsule. During a follow-up examination, 3 nodules were detected by ultrasound in the splenorenal area. This gave reason to suspect tumor recurrence. Considering the possibility of splenosis, a selective spleen scan using denatured red blood cells was performed as a final diagnostic step. This method confirmed the nodules as representing splenic tissue. Splenosis should be included in the differential diagnosis of solid masses in the postsplenectomy patient.

FDG positron emission tomographic, radioiodine, and MIBI imaging in a patient with poorly differentiated insular thyroid carcinoma.

Poorly differentiated insular thyroid carcinoma is now classified as a separate entity among other tumors of the thyroid gland. Its histologic pattern and its clinical course are regarded as intermediate between well differentiated and anaplastic thyroid cancer. Insular carcinoma accumulates I-131, but no data exist regarding its fluorodeoxyglucose (FDG) positron emission tomographic (PET) uptake. The authors report F-18 FDG PET, Tc-99m MIBI, and radioiodine imaging features in a 63-year-old patient with metastatic insular thyroid carcinoma. After total thyroidectomy (for poorly differentiated insular carcinoma pT3a), the patient was referred for radioiodine ablation. No signs of recurrence were present until 16 months later, when thyroglobulin levels increased. An I-131 scan showed a single lesion in the right lung, and further radioiodine treatment was administered (cumulative dose [530 mCi], 19,610 MBq I-131). Three years after the initial diagnosis, FDG-PET and Tc-99m MIBI scans were performed within 5 days during thyroxine treatment. After that, thyroxine substitution was withdrawn; 6 weeks later, an I-131 whole-body scan was performed. Both radioiodine and MIBI images showed increased tracer uptake in the known lung lesion. However, FDG PET showed a normal tracer distribution. Magnetic resonance and computed tomographic imaging confirmed a 12-mm lesion in the right upper lobe. These findings support the concept of the "flip-flop phenomenon" in insular thyroid carcinoma, an alternating pattern of metastases with either I-131 or FDG-uptake. Despite poorly differentiated histologic findings, glucose metabolism was not increased in this patient with an insular tumor.

Does (99m)Tc-Sestamibi in high-grade malignant brain tumors reflect blood-brain barrier damage only?

(99m)Tc-Sestamibi (MIBI) has been successfully applied in recurrent glioblastoma. The aim of this study was to evaluate the incremental diagnostic information of MIBI as a tumor-avid radiopharmaceutical compared with (99m)Tc-pertechnetate ((99m)Tc) as sole indicator of the integrity of the blood-brain barrier. Twenty-five patients with confirmed recurrent brain tumors were included. MIBI SPET was performed 10 min after injection of 555 MBq MIBI intravenously with a triple-headed gamma camera equipped with LE-UHR-PAR collimators over 360 degrees (3 degrees /step) and stored in a 128(2) matrix. Identical acquisition parameters were used for (99m)Tc SPET, which was acquired 3 h after injection of 740 MBq (99m)Tc. Normalized tumor uptake (NU) was calculated from attenuation-corrected transaxial slices. In addition, tumor/plexus, tumor/nasopharynx, and tumor/parotid gland ratios were assessed in both studies. No statistically significant differences were detected for the mean NU of tumor tissue with MIBI (0.26 +/- 0.10) and (99m)Tc (0.39 +/- 0. 33) and for the tumor/nasopharynx and tumor/parotid gland ratios; only the tumor/plexus ratio was significantly higher for (99m)Tc than for MIBI (p < 0.05). In conclusion, our data indicate that MIBI scintigraphy in brain tumors at 10 min postinjection reveals no additional visual information over that provided by the conventional (99m)Tc-pertechnetate brain scan, and in addition, tracer retention reflects primarily blood-brain barrier damage.

ROC analysis of three perfusion display options for ECG-gated perfusion SPECT in severe CAD.

AIM: The simultaneous computation and display of wall motion and perfusion patterns in a single 3D ventricular model would considerably ease the assessment of ECG-gated Tc-99m-sestamibi SPECT, yet the effect on the accuracy of allocating regional perfusion has so far not been validated. METHODS: 3D perfusion mapping (3D Perfusion/Motion Map Software) was compared to the visual assessment of ungated tomographic slices and polar perfusion mapping (Cedars-Sinai PTQ) by correlation analysis and receiver operating characteristics (ROC) analysis at different cut-off levels for coronary stenoses in 50 patients (11 single-, 22 two-, 16 three-vessel disease). Ungated SPECT data were obtained by adding the intervals prior to reconstruction and displaying conventional tomographic slices. All display options were visually assessed in 8 ventricular segments according to a 4-point scoring system and compared to the graded results of coronary angiography. RESULTS: All three display options showed a comparable diagnostic performance for the detection of severe stenoses. The diagnostic gain for the detection of stenoses above 59% was highest for ungated tomographic slices, followed by ungated polar mapping and 3D mapping. Regional assessment revealed a limited performance of 3D mapping in the proximal anterior and distal lateral wall. Polar mapping showed a balanced regional performance. CONCLUSION: 3D Perfusion mapping provides comparable information to conventional display options with the highest diagnostic strength in severe stenoses. Further improvement of the algorithm is needed in the definition of the valve plane.

Scintigraphic assessment of pulmonary and whole-body blood flow patterns after surgical intervention in congenital heart disease.

UNLABELLED: Glenn shunt and Fontan procedure, the most widely used surgical procedures in congenital heart anomalies, may be associated with abnormal pulmonary blood flow patterns and the development of pulmonary arteriovenous fistulae. METHODS: This study quantified pulmonary and whole-body blood flow using the microsphere technique by sequential injection of 99mTc microspheres into upper and lower limb veins and performing planar lung imaging in four projections and anterior and posterior whole-body scans in 46 patients with either Glenn shunt or Fontan procedure. The right-to-left shunt volume was estimated by a brain and kidneys-to-lungs ratio and compared with calculations from the whole-body scans. RESULTS: In 31 of 46 patients, the blood from the superior vena cava was drained preferentially into the right lung (75%+/-19%). The inferior venous system was drained equally into both lungs. The right-to-left shunt volume was 24%+/-12% after injection into the superior caval system, 50%+/-18% after injection into the inferior caval system. A subgroup of patients who had undergone a palliative Blalock-Taussig shunt (BTS) before the final surgery showed a perfusion pattern that was not known after pulmonary angiography or contrast echocardiography: 15 of 24 patients with BTS had hypoperfusion of the upper lobe on the side of the BTS after injection into the arm vein and corresponding normal perfusion or hyperperfusion when injected into the foot vein. CONCLUSION: Lung perfusion scintigraphy after tracer application into the superior and inferior caval systems detects more abnormal pulmonary blood flow patterns than contrast echocardiography and is the only procedure able to quantify right-to-left shunt volume individually for the superior and inferior caval systems. Thus, this diagnostic technique should be part of the routine follow-up in children after Glenn shunt or Fontan procedure.

Acupuncture in the treatment of posttraumatic pain syndrome.

To test the hypothesis that classical Chinese acupuncture provides an additional benefit subjectively as well as objectively in patients suffering from reflex sympathetic dystrophy, a double-blind, placebo-controlled prospective trial was performed. Fourteen patients suffering clinically and scintigraphically from acute CRPS of the upper limb lasting of more than one but less than 6 months were studied. Patients were randomly assigned to either the classical acupuncture (group A) or sham acupuncture (group S), which was applied five times a week for three weeks and required 30 minutes. Both groups received the same defined standard treatment. The current state of pain was assessed by means of a visual analogue scale. Subjective success of treatment was rated by the patients by means of a rating scale. Each patient underwent a clinical examination and was investigated by 5-phase bone scan in order to confirm the diagnosis. The current state of pain as well as clinical parameters were almost identical in patients of group A and of group S at the beginning. During therapy clinical parameters as well as pain improved in both groups and reached nearly normal levels after 6 months. Owing to the small number of patients in our study, no differences between sham and treatment group could be recognized. For a definitive statement the treatment of further patients in both groups is planned. Determinations of the effect of acupuncture on clinical parameters, based on long-term follow-ups are projected.

Anemia and carnitine supplementation in hemodialyzed patients.

Carnitine supplementation in hemodialyzed patients was studied in a double-blinded, randomized, controlled trial in order to elucidate the effect of intravenous carnitine on renal anemia in patients treated with recombinant human erythropoietin (rHuEPO). Twenty stable hemodialysis (HD) patients received intravenous L-carnitine after each dialysis session in a dosage of 5 (N = 15) and 25 (N = 5) mg/kg, respectively, together with intravenous iron saccharate (20 mg/HD session) for four months and without iron for a further four months. Twenty patients received placebo instead of carnitine with an identical iron regimen. After a run-in phase of six months with a stable rHuEPO requirement, the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin levels. At study entry (T0), plasma and red blood cell carnitine levels did not correlate significantly with the rHuEPO requirement. However, plasma free and total carnitine levels showed a significant negative correlation with erythrocyte survival time at T0. After four months of coadministration of intravenous iron and L-carnitine (T4), the rHuEPO requirement decreased in 8 of 19 evaluable HD patients. In these responders, the weekly rHuEPO dose was decreased significantly by 36.9+/-23.3% (183.7+/-131.7 at T0 vs. 126.6+/-127.9 U/kg/week at T4, P < 0.001). The rHuEPO requirement, however, was unchanged when all carnitine-treated patients were compared between T0 and T4 (T0: 172.0+/-118.0 vs. T4: 152.3+/-118.8 U/kg/week, P = 0.07, NS), but the erythropoietin resistance index decreased significantly in this group (T0: 16.0+/-11.0 vs. T4: 13.6+/-10.5 U/kg/week/g of hemoglobin, P < 0.02). The erythrocyte survival time was measured in five HD patients treated with iron and carnitine at T0 and T4. Two out of these patients were carnitine responders and showed an increase of erythrocyte survival time of 15 and 20%, respectively. After the withdrawal of iron supplementation, the rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated patients during four more months. According to our data, L-carnitine, in addition to iron supplementation, may have an effect on erythropoietin resistance and erythrocyte survival time in HD patients. More than half of our patients, however, showed no benefit. Further studies to identify those HD patients who might have a benefit of carnitine supplementation, as well as studies concerning the optimal dosage, duration, and way of administration of carnitine supplementation and its mechanism of action, are required.