Analysis of blood flow and glucose metabolism in mammary carcinomas and normal breast: a H2(15)O PET and 18F-FDG PET study.

OBJECTIVE: To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. METHODS: H2(15)O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. RESULTS: Mean values based on the regions of interest were 59.2+/-43.9 ml x min(-1) x 100 g(-1) (perfusion), 0.58+/-0.26 ml x g(-1) (distribution coefficient), 7.76+/-6.10 (standardized uptake), and 5.4+/-2.5 mg x min(-1) x 100 g(-1) (glucose metabolism). The corresponding values for normal breast tissue were 22.1+/-13.2 ml x min x 100 g(-1) (perfusion), 0.16+/-0.05 ml x g(-1) (distribution coefficient), 0.33+/-0.07 (standardized uptake), and 0.18+/-0.08 mg x min x 100 g(-1) (glucose metabolism). For each tumour-normal tissue parameter pair, the mean values were significantly higher in tumours than normal breast tissue. Region-of-interest and pixel-wise correlation analysis revealed a positive association between glucose metabolism and distribution coefficient and glucose metabolism and perfusion for 7/10 tumours investigated. CONCLUSIONS: H2(15)O PET and 18F-FDG PET were able to differentiate breast cancer and normal breast tissue. The pixel-wise analysis revealed information about the heterogeneity of tumour fine structure in perfusion, distribution coefficient, and glucose metabolism, which may provide important guidelines for improving individual treatment.

Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours.

AIM: High-grade Ewing sarcomas and Primitive neuroectodermal tumours (PNET) make up the tumours of the Ewing family. Our purpose was to evaluate the value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in patients with Ewing tumours. PATIENTS AND METHODS: Twenty-four patients who had PET because of a suspected Ewing tumour during a 5-year period were included in this retrospective study. The images of 33 whole-body FDG PET investigations performed in primary or secondary diagnostics were analysed visually and semi-quantitatively by using standardized uptake values (SUVs). In 14 cases, PET was compared to bone scintigraphy regarding bone lesions. The final diagnosis was based on histology, imaging and follow-up. RESULTS: Histologically, the primary lesions were 10 Ewing sarcoma, 13 PNET and one osteomyelitis. The sensitivity and specificity of an examination-based analysis (presence of Ewing tumour and/or its metastases) were 96 and 78%, respectively. Altogether, 163 focal lesions were evaluated. Sensitivity and specificity regarding individual lesions were 73 and 78%. This lower sensitivity is mainly due to small lesions. In true-positive cases, the mean SUV was 4.54+/-2.79, and the SUVs in two false-positive cases were 4.66 and 1.60. True-positive and false-positive cases could not be differentiated definitively based on SUVs because of overlap and low values in true-positive lesions. In four cases, PET depicted 70 while bone scintigraphy depicted only eight bone metastases. CONCLUSION: An FDG PET investigation is a valuable method in the case of Ewing tumours. PET is superior to bone scintigraphy in the detection of bone metastases of Ewing tumours. For the depiction of small lesions, mainly represented by pulmonary metastases, PET is less sensitive than helical computed tomography. Determination of the role of whole-body FDG PET in diagnostic algorithm needs further investigation.

Cerebral regional hypometabolism caused by propofol-induced sedation in children with severe myoclonic epilepsy: a study using fluorodeoxyglucose positron emission tomography and statistical parametric mapping.

Cerebral positron emission tomography (PET) in children often requires sedation. This study evaluated sedation-associated effects on cerebral glucose metabolism in 30 children with severe myoclonic epilepsy as investigated by cerebral (18)F-fluorodeoxyglucose (FDG)-PET. Prior to the PET acquisition, 24 children underwent propofol sedation. Pixel-based t-statistics were calculated using statistical parametric mapping (SPM99) for comparisons of the patients' PET scans with both a healthy adult control group and an age-matched child intra-group control. In both analyses, statistically significant hypometabolic areas were found in the medial parieto-occipital cortex bilaterally, including the lingual gyrus, cuneus, posterior cingulate and middle occipital gyrus in all sedated children. All these localizations correlated in a covariate analysis with the injected dose of propofol (P<0.01, corrected). The bilateral parieto-occipital hypometabolism is likely to be a sedation-specific effect and should be taken into account when evaluating cerebral FDG-PET scans in sedated children.

Activation of a residual cortical network during painful stimulation in long-term postanoxic vegetative state: a 15O-H2O PET study.

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P<0.05, small-volume-corrected). No additional areas of the complex pain-processing matrix were significantly activated. In conclusion, the regional activity found at the cortical level indicates that a residual pain-related cerebral network remains active in long-term PVS patients.

Comparative diagnostic value and therapeutic relevance of magnetic resonance imaging and bone marrow scintigraphy in patients with metastatic solid tumors of the axial skeleton.

PURPOSE: To evaluate the comparative impact of magnetic resonance imaging (MRI) and bone marrow scintigraphy (BMS) in bone marrow metastases of solid tumors. METHODS: In 20 patients with solid tumors MRI of the axial skeleton and whole-body BMS were retrospectively reviewed. Detectability of metastases, extent of disease and therapeutic implications were assessed. RESULTS: In 15/20 (75%) patients MRI and BMS concordantly revealed bone marrow metastases of the axial skeleton. In nine of these 15 patients (60%) MRI showed more metastases. Local radiotherapy or surgery was performed in seven of these cases (78%). BMS detected additional metastases of the appendicular skeleton in 8/15 (53%) patients. In 4/20 cases (20%) the imaging findings were discordant. In three patients with degenerative changes (n=2) or lipoma (n=1) BMS was false positive. In another patient BMS failed to detect metastases proven by MRI and clinical follow-up resulting in subsequent radiation therapy. One patient had normal bone marrow. CONCLUSION: MRI appears to be more sensitive and specific in the detection of bone marrow metastases in the axial skeleton and is of clinical importance for subsequent local therapy.

Unusual bilateral Tc-99m DPD uptake on bone scan.

A 74-year-old man with prostate cancer was screened for bone metastases. The scan exhibited severe degenerative skeletal changes (especially in the spine and the right knee) and catheter drainage of the bladder, but obviously no bone metastases. Surprisingly, 2 almost symmetric "devil-like"-looking lesions were noted in the frontolateral skull. The patient was treated with bilateral bore hole trepanation because of a subdural hematoma 3 weeks earlier. The lesions can be interpreted as augmented bone metabolism in these regions. Although subdural hematoma is fairly common (incidence, 15:100,000 annually), bilateral trepanation is only performed in approximately 5% of patients.

Can body volume be determined by PET?

PURPOSE: To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. METHODS: Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. RESULTS: In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81+/-15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. CONCLUSION: PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV(LBM)).

SMART-PET: multimodality white matter imaging and display without loss of quantitative information.

PURPOSE: To improve analysis of cerebral white matter (WM) in fluoro-deoxy-glucose positron emission tomography (PET) images. MATERIALS AND METHODS: A multimodality analysis technique (segmented MRI and registered Talairach-transformed PET [SMART-PET]) was used for quantitative assessment of WM metabolism. Data processing included Talairach transformation of three-dimensional magnetic resonance imaging (MRI) and subsequent automated segmentation and coregistration to normalized PET images. Color model transformations were used for combined display: the hue saturation value color model was regarded as a three-dimensional data matrix, integrating quantitative voxel data of both modalities. The technique was applied in normal subjects and in patients suffering from different WM diseases. Regional analysis was performed to classify metabolic impairment on a five-point scale. RESULTS: Using SMART-PET, a considerable gain in image contrast for WM was achieved in all cases. In the normal subjects, WM metabolism was shown to be homogeneously unimpaired. Sum scores of regional analysis revealed metabolic WM changes in all patients. Extent of WM hypometabolism exceeded the extent of the lesions as delineated by MRI signal changes. CONCLUSION: The potential of the method for further elucidation of the role of WM diseases in brain dysfunction in patients is discussed.

18F-DOPA positron emission tomography for the detection of glomus tumours.

The purpose of this study was to evaluate (18)F-DOPA whole-body positron emission tomography ((18)F-DOPA PET) as a biochemical imaging approach for the detection of glomus tumours. (18)F-DOPA PET and magnetic resonance imaging (MRI) were performed in ten consecutive patients with proven mutations of the succinate dehydrogenase subunit D ( SDHD) gene predisposing to the development of glomus tumours and other paragangliomas. (18)F-DOPA PET and MRI were performed according to standard protocols. Both methods were assessed under blinded conditions by two experienced specialists in nuclear medicine (PET) and diagnostic radiology (MRI). Afterwards the results were compared. A total of 15 lesions (four solitary and four multifocal tumours, the latter including 11 lesions) were detected by (18)F-DOPA PET. Under blinded conditions, (18)F-DOPA PET and MRI revealed full agreement in seven patients, partial agreement in two and complete disagreement in one. Eleven of the 15 presumed tumours diagnosed by (18)F-DOPA PET were confirmed by MRI. The correlation of (18)F-DOPA PET and MRI confirmed three further lesions previously only detected by PET. All of them were smaller than 1 cm and had the signal characteristics of lymph nodes. For one small lesion diagnosed by PET, no morphological MRI correlate could be found even retrospectively. No tumour was detected by MRI that was negative on (18)F-DOPA PET. All tumours diagnosed by MRI showed a hyperintense signal on T2-weighted images and a distinct enhancement of contrast medium on T1-weighted images. The mean tumour size was 1.5+/-0.5 cm. (18)F-DOPA PET seems to be a highly sensitive metabolic imaging procedure for the detection of glomus tumours and may have potential as a screening method for glomus tumours in patients with SDHD gene mutations.

3D-Cardiac-PET. A Recommendable Clinical Alternative to 2D-Cardiac-PET?

The objective of this study was to test the clinical practicability of a 3D-cardiac-positron emission tomography(PET) procedure. During preoperative viability diagnostics of the myocardium with fluorine-18-fluorodeoxyglucose(18F-FDG)PET, comparative recordings were made in 2D (ECAT Exact) and 3D Mode (Quest). Ten patients (2 women, 8 men, ages 34-72 years) with coronary artery disease and a known myocardial infarction in the history were examined. Both examinations were made on the same day following single FDG injection. In 9 of the 10 cases, 3 independent examiners arrived at the same diagnoses from the 2D and 3D recordings, whereby only one-third the activity used for 2D exposures was required for 3D acquisition. In one case, the 3D recording showed no accumulation around the anterior wall near the apex, in spite of demonstrated, albeit limited, viability in the 2D mode. The cause of this discrepant finding is assumed to lie in equipment/uptake and patient-related differences in the test configuration. In summary, 3D acquisition offers a promising alternative to 2D recordings in the viability diagnostics of the myocardium based on a considerable reduction in radiation exposure for patients and personnel, as well as reduction in the costs for radiopharmaceuticals. Further evaluation of the method in broader studies would appear necessary.

Non-invasive differentiation of pancreatic lesions: is analysis of FDG kinetics superior to semiquantitative uptake value analysis?

The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (FDG PET) for the non-invasive differentiation of focal pancreatic lesions originating from cancer or chronic pancreatitis by combined visual image interpretation and semiquantitative uptake value analysis has been documented. However, in clinical routine some misdiagnosis is still observed. This is because there is potential overlap between the semiquantitative uptake values obtained for active inflammatory lesions and cancer. Therefore, this prospective study was undertaken to test the hypothesis that analysis of dynamic kinetics of focal pancreatic lesions based on FDG PET may more accurately determine the benign or malignant nature of such lesions. Thirty patients (56+/-17 years) were studied dynamically with FDG PET for a period of 60-90 min. Patients were assigned to one of four groups: control, acute pancreatitis, chronic pancreatitis or pancreatic cancer. Two observers, blinded to the clinical data, analysed the time-activity curves of FDG kinetics based on region of interest analysis. The diagnosis predicted by FDG PET was compared with the result of histological examination of the surgical specimen. Analysis of FDG kinetics revealed significant differences in the shape of the time-activity curve for controls, pancreatic cancer and inflammatory disease. Surprisingly, there was no significant difference in the time-activity curve shape for chronic pancreatitis and acute pancreatitis; this is, however, not a clinical issue. Furthermore, acquisition time (60 min vs 90 min) did not affect interpretation of the time-activity curve, so that scanning time may be regularly shortened to 60 min. Interobserver agreement was 1. Based on these findings, non-invasive differentiation between pancreatic cancer and chronic pancreatitis was correctly predicted in all cases, as confirmed by histology. In addition, the specificity was increased compared with that obtained from standardised uptake value analysis. Non-invasive differentiation between pancreatic cancer and chronic pancreatitis may best be achieved based on a dynamic FDG PET study including kinetic analysis. This approach yields results superior to those obtained from a semiquantitative analysis of pancreatic lesions.

High social desirability and prefrontal cortical activity in cancer patients: a preliminary study.

BACKGROUND: Social desirability is sometimes associated with poor prognosis in cancer patients. Psycho-neuro-immune interaction has been hypothesized as an underlying mechanism of the negative clinical outcome. Purpose of this study was to examine possible effects of high social desirability on the regional brain activity in patients with malignant diseases. MATERIAL/METHODS: Brain metabolism of 16 patients with various malignant diseases was measured by PET with 18F-fluorodeoxyglucose (FDG). Patients were divided into 2 groups using median split on Marlowe & Crown's Social Desirability Scale (MC), controlling for age, gender, and for severity of depression and anxiety, the possible two major influential factors. A group comparison of the regional cerebral activity was calculated on a voxel-by-voxel basis using statistical parametric mapping (SPM). RESULTS: The subgroup comparison showed that the high social desirability was associated with relatively increased metabolism in the cortical regions in the prefrontal, temporal and occipital lobes as well as in the anterior cingulate gyrus. CONCLUSIONS: High social desirability seems to be associated with increased activity in the prefrontal and other cortical areas. The finding is in an accordance with previous studies that demonstrated an association between prefrontal damage and anti-social behavior. Functional neuroimaging seems to be useful not only for psychiatric evaluation of major factors such as depression and anxiety but also for further psychosocial factors in cancer patients.

Pheochromocytomas: detection with 18F DOPA whole body PET--initial results..

PURPOSE: To evaluate fluorine 18 ((18)F) dihydroxyphenylalanine (DOPA) whole-body positron emission tomography (PET) as a biochemical imaging approach for detection of pheochromocytomas. MATERIALS AND METHODS: (18)F DOPA PET and magnetic resonance (MR) imaging were performed in 14 consecutive patients suspected of having pheochromocytomas (five sporadic, nine with von Hippel-Lindau disease); metaiodobenzylguanidine (MIBG) scintigraphy was performed in 12 of these patients. The individual imaging findings were assessed in consensus by specialists in nuclear medicine and radiologists blinded to the results of the other methods. The findings of the functional imaging methods were compared with those of MR imaging, the reference standard. Histologic verification could be obtained in eight patients with nine tumors. RESULTS: Seventeen pheochromocytomas (11 solitary, three bifocal; 14 adrenal, three extraadrenal) were detected with MR imaging. (18)F DOPA PET and MR imaging had concordant results in all 17 tumors. In contrast, MIBG scintigraphy had false-negative results in four patients with three adrenal tumors smaller than 2 cm and one extraadrenal tumor with a diameter of 3.6 cm. On the basis of these data, sensitivities of 100% for (18)F DOPA PET and of 71% for MIBG scintigraphy were calculated. Specificity was 100% for both procedures. CONCLUSION: (18)F DOPA PET is highly sensitive and specific for detection of pheochromocytomas and has potential as the functional imaging method of the future.