Anton Staudenherz

Comparison and histopathological correlation of three parathyroid imaging methods in a population with a high prevalence of concomitant thyroid diseases

The aim of this prospective study was to evaluate the diagnostic utility of a technetium-99m sestamibi dual-phase protocol enhanced by single-photon emission tomography (SPET) and semiquantitative analysis in comparison to established preoperative staging procedures in patients with primary hyperparathyroidism. Twenty-eight (50%) out of 56 patients had superimposed thyroid disease, and 12 patients had previously undergone neck surgery. Visual and semiquantitative analysis of planar99mTc-sestamibi dual-phase imaging, SPET of the delayed phase, ultrasonography, and thallium-201 chloride-technetium-99m pertechnetate subtraction scintigraphy was further correlated with the histopathological examination of the surgical specimens.99mTc-sestamibi dual-phase imaging achieved the highest sensitivity for side localization and precise localization compared with201Tl-99mTc subtraction scintigraphy and ultrasonography, but the differences reached statistical significance only in comparison to ultrasonography. Semiquantitative analysis did not enhance sensitivity. Adenoma detection by99mTc-sestamibi dual-phase imaging was only correlated to serum calcium levels and osteocalcin, not to cell density or oxyphil cell count (SPET yielded additional information for the exact topographical localization of the parathyroid tumour in 22 (39%) patients with superimposed thyroid disease or previous neck surgery but did not enhance the overall detection rate.

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.

Pattern recognition in five-phase bone scintigraphy: diagnostic patterns of reflex sympathetic dystrophy in adults

The objective of this study was to assess qualitative and quantitative patterns of tracer accumulation to increase the diagnostic utility of bone scintigraphy in reflex sympathetic dystrophy (RSD). Of 120 patients with high clinical suspicion for RSD, 96 were confirmed as having RSD during follow-up, while the remaining 24 were used as controls. Clinical parameters were measured and correlated to five activity ratios (0–30 s, 0.5–5 min, 5–15 min, 3 h, 24 h) and five scintigraphic signs. Monitoring three dynamic phases revealed different tracer kinetics of potential diagnostic utility; however, the 24-h bone phase offered no additional diagnostic contribution and can be omitted. Quantification provided objective parameters for the duration of symptoms, pain and impairment of movement but not for surface temperature differences, swelling and impairment of physical force. It is of limited use for diagnosis except for the exclusion of disease. Discriminant analysis revealed the combination of three signs (diffuse uptake in carpus/tarsus+diffuse uptake in all small joints+increased activity ratio in the late blood pool phase) to be the pattern with the highest diagnostic accuracy independent of localisation, sex, age and precipitating factors. It is concluded that the scintigraphic confirmation of RSD is based on lateralisation in the late blood pool phase and the described pattern in the early bone phase.

Concomitant hyperparathyroidism and nonmedullary thyroid cancer, with a review of the literature.

Purpose Primary hyperparathyroidism and concomitant thyroid cancer is a rare and complicated setting for diagnostic imaging. Materials and Methods The authors report the accidental finding of primary hyperparathyroidism in a patient with rapid enlargement of a thyroid nodule and the results of a literature review. Results Tl-201–Tc-99m subtraction scintigraphy correctly revealed the malignant nature of a large cold thyroid nodule and mediastinal parathyroid hyperplasia. In contrast, high-resolution ultrasound indicated a retrothyroidal hyperplastic parathyroid gland. Surgery followed the findings of the preoperative ultrasound and intraoperative biopsy, yet hyperparathyroid disease persisted. Repeated scintigraphy confirmed an ectopic parathyroid gland, which was resected from a paraesophageal location. Subsequently, hormone and calcium levels returned to normal and remained normal during a follow-up period of 3 years. A literature review revealed a prevalence of approximately 3% of nonmedullary thyroid cancer, which was found in patients operated on for primary hyperparathyroidism. Previous neck irradiation, especially in childhood, appears to be a risk factor for the development of both nonmedullary thyroid carcinoma and for primary hyperparathyroid disease. Conclusions This case illustrates the need for clinical awareness of concomitant hyperparathyroidism and nonmedullary thyroid cancer and is substantiated with published case reviews. The preoperative scintigraphic localization of hyperfunctioning parathyroid tissue, although not advised as a routine procedure, may provide diagnostic information in addition to high-resolution ultrasound and intraoperative biopsy. In addition, scintigraphy can be useful even in the technically difficult setting of concomitant thyroid cancer.

Does 99mTc-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.

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

PurposeA 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.MethodPatterns 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 ≥50xa0% reduction in post induction score compared with baseline.ResultsIn total, 1968 image sets were reviewed individually. Response rates of 88xa0% and 82xa0% were recorded for patients with baseline skeletal scores ≤23 and 24-48 respectively, compared with 44xa0% response in patients with skeletal scores >48 (pu2009=u20090.02). 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.ConclusionsThe 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.

Hybrid PET/CT and SPECT/CT Imaging

1.1 Definition of nuclear medicine, molecular imaging and hybrid imaging Nuclear Medicine uses radioactive probes commonly referred to as tracers for the diagnosis and treatment of diseases. Monitoring the metabolic fate of nanomolar amounts of radiolabeled substances by tracking their photon emission with SPECT (Single Photon Emission Tomography) and PET (Positron Emission Tomography) was the first widely practiced branch of Molecular Imaging (MI). MI is the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems (Mankoff, 2007). Among the different techniques summarized in MI, tracer imaging in Nuclear Medicine has the highest molecular sensitivity, tracing substances in the 10E-3 to 10E-5 mol/l range. Conventional imaging with x-ray was primarily used as a snapshot of anatomy and depicts tissue by its physical characteristics (e.g., X-ray density). Contrast agents in CT are used to increase the visibility of vessels and organ surfaces. Functional information is at best limited to that of perfusion and permeability. This is one of the most significant differences between Radiology and Nuclear Medicine. The advantage of functional imaging is that of increasing sensitivity because metabolic changes precede anatomical changes and can be detected long before structural changes appear. Functional imaging, however, has a low specificity in distinctly different pathologies (e.g., degenerative, inflammatory or malignant bone lesions) if they are visualized by unspecific common properties as hyperaemia, increased regional tracer permeability and osteoplastic metabolism. To overcome this and to increase specificity, highly specific probes (e.g., receptor imaging) have been developed. With minimal uptake outside the targeted tissues, specific probes offer little information about the surrounding tissues and consequently do not provide the topographical information needed by surgeons or therapy planning systems in radio oncology. The advantage of anatomical imaging by CT is its high anatomical resolution and usually good topographical information. On the other hand it is a poor predictor of the functional consequences of a finding (e.g., borderline stenosis in coronary CT angiography) and consequently a poor predictor of prognosis. Structural data do not necessarily correlate with the metabolic status of disease and they have a limited diagnostic sensitivity in cases with abnormal anatomy (e.g., scar versus residual tumour). Anatomic tumour response metrics (WHO criteria, Response Evaluation Criteria in Solid Tumours (RECIST)) are insufficient to predict therapy response, particularly in assessing the activity of newer cancer therapies that stabilize disease and may

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.

Reflex sympathetic dystrophy after arthroscopy.

Reflex sympathetic dystrophy (RSD) is a pain syndrome of unknown cause with well-defined clinical features that usually develop after minor or major trauma of a limb. Clinical symptoms include pain, swelling, changes in surface temperature, and an impairment of physical force and mobility. Among other trauma, arthroscopic procedures are known to precipitate RSD. In some patients, making differential diagnoses of complications after arthroscopy and RSD can be difficult based on clinical data. Multiphase bone scintigraphy is exceptionally useful in this setting, because the scintigraphic abnormalities in RSD, in contrast to all other differential diagnoses, are not limited to the site of the trauma and usually affect the entire extremity. This is fully illustrated by the case of a 45-year-old man in whose knee joint burning pain developed 1 week after an initially uncomplicated knee arthroscopy. The findings of initial scans and follow-up results during therapy are described.

Evaluation of [18F]-FDG-Based Hybrid Imaging Combinations for Assessment of Bone Marrow Involvement in Lymphoma at Initial Staging

The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet.