123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi-quantitative reporting ,method by an international panel.

PURPOSE: A robust method is required to standardise objective reporting of diagnostic 123I-mIBG images in neuroblastoma. Prerequisites for an appropriate system are low inter- and intra-observer error and reproducibility across a broad disease spectrum. We present a new reporting method, developed and tested for SIOPEN by an international expert panel. METHOD: Patterns of abnormal skeletal 123I-mIBG uptake were defined and assigned numerical scores [0-6] based on disease extent within 12 body segments. Uptake intensity was excluded from the analysis. Data sets from 82 patients were scored independently by six experienced specialists as unblinded pairs (pre- and post-induction chemotherapy) and in random order as a blinded study. Response was defined as ≥50 % reduction in post induction score compared with baseline. RESULTS: In total, 1968 image sets were reviewed individually. Response rates of 88 % and 82 % were recorded for patients with baseline skeletal scores ≤23 and 24-48 respectively, compared with 44 % response in patients with skeletal scores >48 (p = 0.02). Reducing the number of segments or extension scale had a small but statistically negative impact upon the number of responses detected. Intraclass correlation coefficients [ICCs] calculated for the unblinded and blinded study were 0.95 at diagnosis and 0.98 and 0.99 post-induction chemotherapy, respectively. CONCLUSIONS: The SIOPEN mIBG score method is reproducible across the full spectrum of disease in high risk neuroblastoma. Numerical assessment of skeletal disease extent avoids subjective evaluation of uptake intensity. This robust approach provides a reliable means with which to examine the role of 123I mIBG scintigraphy as a prognostic indicator in neuroblastoma.

[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.

Measurement of renal function in patients with Fabry disease.

UNLABELLED: Appropriate measurement of the glomerular filtration rate (GFR) is important for the assessment of renal function. This paper reviews the methods used to assess GFR in clinical trials of enzyme replacement therapy (ERT) in patients with Fabry disease, which include inulin clearance, 24-hour creatinine clearance, chromium ethylene diamine tetraacetate (51Cr-EDTA) clearance and cystatin C concentrations. GFR has also been estimated using calculations based on creatinine clearance (the Cockcroft-Gault formula) and the Modification of Diet in Renal Disease (MDRD) equation. Analysis of the results of these studies shows that there are striking discrepancies between estimated and measured GFR. For example, the MDRD equation overestimates GFR in patients with Fabry disease who have normal renal function. In addition, cystatin C has been shown to be of limited use for measuring renal function during ERT, because it is influenced by other factors such as age, gender and weight. CONCLUSION: The use of exact methods, such as inulin clearance, 124I-iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol, appears to be mandatory for a robust evaluation of the effects of ERT on GFR in patients with Fabry disease.

Differential diagnosis of atypically located single or double hot spots in whole bone scanning.

UNLABELLED: Our study assessed the predictive value of atypically located hot spots in routine 99mTc-DPD (3,3 diphosphono-1, 2-propane dicarboxylic acid tetrasodium salt) bone scanning for osseous tumor spread in patients with a history of malignant tumor. METHODS: Of 1286 scans in consecutive patients with a history of malignant tumor, but with no current evidence of osseous tumor spread, 172 displayed one or two hot spots in the following locations: transverse process of a single vertebra, manubriosternal junction, unilateral process of L5/S1, unilateral shoulder, costal cartilage, single rib, and unilateral sternoclavicular joint. The final diagnosis could be established by a control bone scan after at least 6 mo, biopsy and/or postmortem, respectively, in 135 patients. RESULTS: Of the atypical hot spots, 11.1% were the first indication for osseous tumor spread. This diagnosis was most probable for single hot spots in the rib (25%) and shoulder (21%). Conversely, hot spots in the sternoclavicular joint never indicated malignancy. CONCLUSION: The likelihood of atypically located isolated hot spots indicating osseous tumor spread is higher than expected during routine investigations in patients with a history of malignant tumor but no current evidence for malignant disease. Only hot spots in the sternoclavicular joint did not indicate metastatic disease in our study.

Heterogeneity of myocardial perfusion provides the physiological basis of perfusable tissue index.

UNLABELLED: Assessment of viable from nonviable myocardium is critical for the care of patients being considered for revascularization procedures. Recently, the perfusable tissue index (PTI) has been proposed as an index of myocardial viability. METHODS: Computer simulations were performed for homogeneously and heterogeneously perfused tissue over a wide range of flows (0.04-6.4 ml/g/min) using both bolus and infusion inputs. RESULTS: PTI estimated from simulated homogeneously perfused tissue did reflect the amount of tissue being perfused independent of absolute level of flow, type of input or model configuration, whereas PTI obtained from simulated heterogeneously perfused tissue was consistently lower than the simulated "true" PTI and varied with flow, type of input function and model configuration. Flow estimated with 15O-water was not significantly different from that measured with radio labeled microspheres. CONCLUSION: Oxygen-15-water can diffuse into both acutely and chronically ischemic myocardium irrespective of its functional status. The results suggest that PTI is most likely an index of the heterogeneity of myocardial flow rather than an index of the amount of tissue being perfused. Its utility for delineating myocardial viability is thus related to the amount of tissue perfused that has low absolute levels of perfusion or high degrees of flow heterogeneity.

Scintigraphic pitfalls in giant parathyroid glands.

We report a case of hyperparathyroidism with surgically confirmed bilaterally enlarged parathyroid glands mimicking a normal thyroid gland. Technetium-99m-pertechnetate-201Tl chloride subtraction scintigraphy was inconclusive because of suppressed thyroidal [99mTc]pertechnetate uptake after coronary angiography. Technetium-99m-sestamibi double-phase scintigraphy showed homogeneous 99mTc-sestamibi uptake that mimicked a normal thyroid gland and no differential washout, thus leading to an erroneous visual interpretation of a normal scan. Semiquantitative assessment of tracer washout, however, can differentiate between normal thyroid tissue and symmetrical parathyroid uptake mimicking normal thyroid tissue. We conclude that semiquantitative assessment of tracer washout increases the diagnostic sensitivity of 99mTc-sestamibi double-phase scintigraphy if: (a) the interpreter is unaware of the anatomical situation, (b) the scintigraphic delineation of the thyroid is hampered by a blocked tracer uptake or (c) the visual interpretation reveals no differential washout in the neck region.

Utility of technetium-99m-sestamibi to assess osseous tumor spread.

We report the staging results and the surgical outcome of a male patient with squamous-cell carcinoma in the floor of the mouth and a bone SPECT scan suggestive of local tumor infiltration of the mandible. Additional 99mTc-sestamibi SPECT imaging of the primary tumor and superimposing of both studies excluded osseous tumor spread and less extensive surgery was performed. Pathohistological examination confirmed the scintigraphic results and indicated a nonspecific periostal reaction as the cause of the positive bone scan. Nevertheless, a high-resolution camera and careful superimposition of both studies is mandatory if the differential diagnosis of an osseous tumor spread of a malignant tumor in the floor of the mouth and possibly less extensive surgery is at stake.

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Frequency of diagnostic dilemmas in 131I whole body scanning.

AIM: The specific excretion pathways of iodine may cause several diagnostic pitfalls. Information concerning their relative frequency and possible consequences in daily routine is scarce. METHODS: A total of 500 (131)I whole-body scans from 300 consecutive patients with differentiated thyroid cancer of two centers were analyzed. The reports were validated with other diagnostic findings during follow-up for 12 to 85 months. 126 scans (25.2%) were performed at the time of discharge after high dose (131)I therapy (2960-11100 MBq). Residual activity was approximately 185 MBq (131)I at the time of imaging. 374 scans (74.8%) were performed in ambulatory patients 48 h after oral administration of 74 MBq (131)I. All patients revealed TSH concentrations >35 micro U/ml. RESULTS: A computerized literature search revealed 74 entities that may cause a false-positive whole body scan, from which 12 were present in our cohort. The uptake patterns could be epitomized into nine clinical settings. Apart from the significantly higher frequency of cervical activity in residual thyroid tissue in patients after high dose therapy no statistically significant difference was found between high and low dose patients. The most frequent combination was stomach and colon activity, which was seen in 15.3% of all scans. Additional images or diagnostic procedures were necessary in 59.3%. Only one patient with a kidney metastasis was initially misinterpreted. The major clinical problems included: contamination, superimposed intestinal retention, hot nose, isolated peripheral metastasis, unexpected breast activity and kidney metastasis. CONCLUSION: (131)I whole-body scanning has to be performed with painstaking precision and full awareness of even the rarest pitfalls in order to remain a sensitive and specific technique for diagnosing metastases from differentiated thyroid carcinoma.

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.

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.

Diagnostic patterns for bone marrow oedema syndrome and avascular necrosis of the femoral head in dynamic bone scintigraphy.

This study used logistic regression analysis to assess qualitative patterns of tracer accumulation in an attempt to improve the diagnostic utility of bone scintigraphy for the detection of the bone marrow oedema syndrome (BMOS) and avascular necrosis (AVN) of the femoral head. Forty-eight symptomatic patients aged 44 +/- 9 years (mean +/- S.D.) with a final diagnosis of AVN (n = 29 hips), BMOS (n = 22), nine other hip disorders or a normal hip were examined with dynamic bone scintigraphy and qualitatively assessed for 11 scintigraphic signs in four phases by three blinded investigators. The accuracy for a correct diagnosis based on individual experience was 60-61% for the three observers, even if different signs were emphasized. A cold spot in the femoral head in both blood pool phases and the bone phase was seen only in 24% of AVN hips. Diffuse tracer accumulation in the femoral head, neck and the intertrochanteric region in the blood pool phases was seen only in 36% of BMOS hips. The arterial phase and the finding of a normal acetabulum in the bone phase had no diagnostic utility in this study. The presence of uptake increased the accuracy of differentiating AVN and BMOS from other disorders or normal hips to 88%. AVN could be differentiated from BMOS with an accuracy of 86% if the signs of the femoral head and inter-trochanteric uptake were combined into a diagnostic pattern. The scintigraphic pattern described increases the diagnostic accuracy of planar dynamic bone scintigraphy for BMOS and AVN.

The diagnostic value of planar and SPET scintimammography in different age groups.

Planar scintimammography (SMM) with 99Tcm-sestamibi (99Tcm-MIBI) has proved to be a useful method in the evaluation of breast lesions. The aim of our study was to determine the diagnostic value of planar and single photon emission tomograpic (SPET) SMM in different age group. We investigated women with breast lesions for which the surgeon recommended biopsy or careful follow-up. Seventy consecutive patients underwent supine planar SMM, while supine SPET was performed in 68 of the patients. Twenty-seven carcinomas in 23 patients and 35 benign lesions in 31 patients were confirmed histologically. In the remaining 16 patients, the findings were classified as benign at follow-up. The carcinomas and benign lesions had a mean (+/- S.D.) diameter of 25 +/- 17 and 17 +/- 11 mm respectively (P < 0.05). A sensitivity/specificity of 67/96% and 88/91% was obtained with the planar and SPET techniques respectively. The accuracy of both techniques was 90%. In patients aged 40 years or less, SPET increased the sensitivity from 50 to 100% (P < 0.01), whereas it decreased the specificity and accuracy from 94 to 81% and 91 to 81% respectively (N.S.). In patients aged 41-50 years, the sensitivity increased from 63 to 100% (P < 0.01), whereas there was a small decrease in specificity and an increase in accuracy (from 91 to 89% and 86 to 91% respectively, N.S.) We conclude that, in younger patients, a negative SPET SMM study indicates the need for careful follow-up rather than biopsy. However, the addition of SPET in supine scintimammography does-not change the overall accuracy significantly.

Effectiveness of coronary heart disease risk management in high-risk patients.

The purpose of this study was to investigate the efficacy of the patient-based coronary heart disease (CHD) risk management strategy in general practice by analyzing patients who were sent to a specialized center as refractory to conventional treatment. Of the 452 patients studied, 152 were excluded because of secondary hyperlipidemia. The effects of a food protocol-monitored dietary/drug treatment on lipid profiles and CHD risk indices and the compliance to this approach were monitored for 12 months in 300 of 452 patients. CHD risk classification was performed according to NIH criteria by the referring physicians, but secondary hyperlipidemia was not identified and treated appropriately. Physicians did not fully utilize dietary and drug treatment and referred the patients to a specialized center too early. The initiated food protocol-controlled treatment was more efficient than pretreatment in general practice, with a compliance of 80.3% by patients selected according to their CHD risk. Long-term CHD risk reduction was persistent for 12 months in compliant patients; however, a cumulative dropout rate of 43% after 6 months and of 68% after 12 months was noted. Statistical analysis failed to reveal consistent prognostic factors of long-term compliance.

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.

[A retrospective referral analysis in nuclear medicine]. / Zuweisungen in der nuklearmedizinischen Diagnostik. Retrospektive Analyse.

AIM: Written reports are the basis of collaboration between clinician and radiologist or nuclear medicine specialist. For clinicians it is important to receive useful and accurate reports that answer their questions. A thorough referral note is needed in order to choose an appropriate examination method and to write a good report. METHODS: In this retrospective study we analyzed 1330 referral notes which were addressed to the Department of Nuclear Medicine at the University Clinic of Nuclear Medicine in Vienna between 2008 and 2011. Examinations were divided into 7 groups (heart, lung, bones, central nervous system, PET or PET-CT and other). The following aspects were studied: diagnosis, clinical question, overall legibility, handwritten/typed, contact information, legibility of the referring doctor's name, internal/external referral, additional information and region to be examined. RESULTS: 18% of the referrals per year were analyzed. A diagnosis was given in 95%, a clinical question in 73%. Additional information was found in 41%. Only 4% were typed. In nearly all of these aspects there were major differences when compared in the seven different groups. CONCLUSION: To generate a good report and to provide optimal conditions for examination the data in the referral note should be given as exact as possible. Our retrospective analysis demonstrated the lack of referral note related information concerning the clinical question. In order to achieve good results, intelligent computer-assisted referrals might lead to better referral notes.

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-induced hypophosphatemic rickets in an adolescent boy--clinical presentation, diagnosis, and histological findings in growth plate and muscle tissue.

CONTEXT: The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported. PATIENT: A mesenchymal tumor was detected in the left distal fibula by (68)Ga-DOTATOC in a 17-yr-old boy with adolescent onset of severe hypophosphatemic rickets. Disabling muscle weakness improved within days after surgery, and normal mobility was restored within months. METHODS AND RESULTS: The resected tissue included part of the growth plate allowing immunohistochemical investigation. Positive staining of FGF23 was found in the tumor cells and in hypertrophic chondrocytes, osteoblasts, and osteoclasts of the adjacent growth plate. This distribution matched that found in growth plate tissue of a healthy control. We found positive staining for the somatostatin receptor not only in the tumor but also within the growth plate and adjacent bony tissue in the patient and the healthy control. Muscle tissue provided evidence for a partial defect in respiratory chain complexes I-IV. Biochemical markers were nearly or completely restored to normal 12 months after surgery. CONCLUSIONS: Hypertrophic growth plate chondrocytes are a target or source of FGF23 in tumor-induced osteomalacia. Low serum phosphate, FGF23, or other factors produced by the tumor may interfere with mitochondrial function.