Automated procedure assessing the accuracy of HRCT-PET registration applied in functional virtual bronchoscopy.

BACKGROUND: Bronchoscopy serves as direct visualisation of the airway. Virtual bronchoscopy provides similar visual information using a non-invasive imaging procedure(s). Early and accurate image-guided diagnosis requires the possible highest performance, which might be approximated by combining anatomical and functional imaging. This communication describes an advanced functional virtual bronchoscopic (fVB) method based on the registration of PET images to high-resolution diagnostic CT images instead of low-dose CT images of lower resolution obtained from PET/CT scans. PET/CT and diagnostic CT data were collected from 22 oncological patients to develop a computer-aided high-precision fVB. Registration of segmented images was performed using elastix. RESULTS: For virtual bronchoscopy, we used an in-house developed segmentation method. The quality of low- and high-dose CT image registrations was characterised by expert's scoring the spatial distance of manually paired corresponding points and by eight voxel intensity-based (dis)similarity parameters. The distribution of (dis)similarity parameter correlating best with anatomic scoring was bootstrapped, and 95% confidence intervals were calculated separately for acceptable and insufficient registrations. We showed that mutual information (MI) of the eight investigated (dis)similarity parameters displayed the closest correlation with the anatomy-based distance metrics used to characterise the quality of image registrations. The 95% confidence intervals of the bootstrapped MI distribution were [0.15, 0.22] and [0.28, 0.37] for insufficient and acceptable registrations, respectively. In case of any new patient, a calculated MI value of registered low- and high-dose CT image pair within the [0.28, 0.37] or the [0.15, 0.22] interval would suggest acceptance or rejection, respectively, serving as an aid for the radiologist. CONCLUSION: A computer-aided solution was proposed in order to reduce reliance on radiologist's contribution for the approval of acceptable image registrations.

Q-Bot: automatic DICOM metadata monitoring for the next level of quality management in nuclear medicine.

BACKGROUND: Regular and precise inspection of the realization of the local nuclear medicine standard operation procedures (SOPs) is very complex and time-consuming, especially when large amount of patient data is obtained from a wide scale of different scan procedures on a daily basis. DICOM metadata comprise a complete set of data related to the patient and the imaging procedure, and consequently all information necessary to evaluate the compliance with the actual SOP. METHODS: Q-Bot, an automatic DICOM metadata monitoring tool which is capable to verify SOP conformities, was tested for 11 months at two nuclear medicine departments. Relevant parameters, such as patient ID, patient mass and height, injected activity, and uptake time, were investigated in the case of adult 18F-FDG whole-body PET/CT and 99mTc-MDP gamma camera bone scans on a daily basis. Q-Bot automatically inspected the actual SOP compliance of these relevant DICOM parameters. Q-Bot graphical user interface (GUI) provided a summary of the outliers in a table format to be investigated by a dedicated technologist. In addition, information related to the error handling was also collected for retrospective analysis of long-term tendencies. RESULTS: In total, 6702 PET/CT and 2502 gamma camera scans were inspected, from which 8581 were confirmed as valid patient study without errors. Discrepancies related to the lack of a parameter, not appropriate format, or improper scan procedures were found in 623 cases, and 156 out of these were corrected before the medical reading and reporting. SOP non-conformities explored with Q-Bot were found to be non-correctable in 467 cases. Systematic errors to our practice turned out to be the manual radiopharmaceutical injection, the allowance to use both SI and non-SI units, and the clear definition of decimal point symbol to use. CONCLUSION: The daily evaluation of Q-Bot results provided early detection of errors and consequently ensured the minimization of error propagation. Integration of a QM software that inspects protocol compliance at a nuclear medicine department provides significant support to detect non-conformities for technologists, and much higher confidence in image quality for physicians.

OAR sparing 3D radiotherapy planning supported by fMRI brain mapping investigations.

The human brain as an organ has numerous functions; some of them can be visualized by functional imaging techniques (e.g., functional MRI [fMRI] or positron emission tomography). The localization of the appropriate activity clusters requires sophisticated instrumentation and complex measuring protocol. As the inclusion of the activation pattern in modern self-tailored 3D based radiotherapy has notable advantages, this method is applied frequently. Unfortunately, no standardized method has been published yet for the integration of the fMRI data into the planning process and the detailed description of the individual applications is usually missing. Thirteen patients with brain tumors, receiving fMRI based RT planning were enrolled in this study. The delivered dose maps were exported from the treatment planning system and processed for further statistical analysis. Two parameters were introduced to measure the geometrical distance Hausdorff Distance (HD), and volumetric overlap Dice Similarity Coefficient (DSC) of fMRI corrected and not corrected dose matrices as calculated by 3D planning to characterize similarity and/or dissimilarity of these dose matrices. Statistical analysis of bootstrapped HD and DSC data was performed to determine confidence intervals of these parameters. The calculated confidence intervals for HD and DSC were (5.04, 7.09), (0.79, 0.86), respectively for the 40 Gy and (5.2, 7.85), (0.74, 0.83), respectively for the 60 Gy dose volumes. These data indicate that in the case of HD < 5.04 and/or DSC > 0.86, the 40 Gy dose volumes obtained with and without fMRI activation pattern do not show a significant difference (5% significance level). The same conditions for the 60 Gy dose volumes were HD < 5.2 and/or DSC > 0.83. At the same time, with HD > 7.09 and/or DSC < 0.79 for 40 Gy and HD > 7.85 and/or DSC < 0.74 for 60 Gy the impact of fMRI utilization in RT planning is excessive. The fMRI activation clusters can be used in daily RT planning routine to spare activation clusters as critical areas in the brain and avoid their high dose irradiation. Parameters HD (as distance) and DSC (as overlap) can be used to characterize the difference and similarity between the radiotherapy planning target volumes and indicate whether the fMRI delivered activation patterns and consequent fMRI corrected planning volumes are reliable or not.

[Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long-term follow-up results]. / Az FDG-PET prognosztikai értéke Hodgkin-lymphomás betegek követésében - hosszú távú eredményeink.

UNLABELLED: In the past few decades Hodgkin lymphoma (HL) has become a highly curable malignant disease, as a result of using modern polychemotherapy and irradiation. Differentiation of active tumor from fibrosis or necrosis within residual radiographic masses represents a problem of interpretation. AIMS: The aim of this retrospective study is to assess the value of FDG-PET for prediction of remission or relapse in HL. PATIENTS AND METHODS: Data of 128 patients, who had residual masses on CT after completion of their planned treatment, have been analyzed. FDG-PET was performed between January 1995 and February 2005. RESULTS: The median duration of the follow-up from PET was 75.5 months (range: 20-180 months). 89 (70%) patients had negative and 39 (30%) patients had positive FDG-PET results. The numbers of true-positive, true-negative, false-positive and false-negative subjects were 29, 83, 10 and 6, respectively. Sensitivity of post-treatment FDG-PET was 83%, specificity 93%, positive predictive value 74%, negative predictive value 93%, and accuracy 88%. The difference between the event free survival of PET positive and negative cases is highly significant (p = 0.0000), according to the Mantel-Cox test. CONCLUSION: Our results, in accordance with literature, clearly indicate that patients with negative FDG-PET results are unlikely to progress or relapse during a long follow-up. However, false positive uptake is a problem. We have investigated the effect of age, histological subtype, clinical stage and the type of treatment on the accuracy, but on the basis of these facts we could not find any significant difference. However, the date of the investigation influenced the results: before 2000 the number of false results was significantly higher than after that time, which shows the importance of investigators' experience.

Activity painting: PET images of freely defined activity distributions applying a novel phantom technique.

The aim of this work was to develop a novel phantom that supports the construction of highly reproducible phantoms with arbitrary activity distributions for PET imaging. It could offer a methodology for answering questions related to texture measurements in PET imaging. The basic idea is to move a point source on a 3-D trajectory in the field of view, while continuously acquiring data. The reconstruction results in a 3-D activity concentration map according to the pathway of the point source. A 22Na calibration point source was attached to a high precision robotic arm system, where the 3-D movement was software controlled. 3-D activity distributions of a homogeneous cube, a sphere, a spherical shell and a heart shape were simulated. These distributions were used to measure uniformity and to characterize reproducibility. Two potential applications using the lesion simulation method are presented: evaluation in changes of textural properties related to the position in the PET field of view; scanner comparison based on visual and quantitative evaluation of texture features. A lesion with volume of 50x50x50 mm3 can be simulated during approximately 1 hour. The reproducibility of the movement was found to be >99%. The coefficients of variation of the voxels within a simulated homogeneous cube was 2.34%. Based on 5 consecutive and independent measurements of a 36 mm diameter hot sphere, the coefficient of variation of the mean activity concentration was 0.68%. We obtained up to 18% differences within the values of investigated textural indexes, when measuring a lesion in different radial positions of the PET field of view. In comparison of two different human PET scanners the percentage differences between heterogeneity parameters were in the range of 5-55%. After harmonizing the voxel sizes this range reduced to 2-16%. The general activity distributions provided by the two different vendor show high similarity visually. For the demonstration of the flexibility of this method, the same pattern was also simulated on a small animal PET scanner giving similar results, both quantitatively and visually. 3-D motion of a point source in the PET field of view is capable to create an irregular shaped activity distribution with high reproducibility.

Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells.

AIM: To establish the effects of Na(+)/Ca(2+) exchanger (NCX) blockers on 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) and (11)C-choline accumulation in different cancer cells. METHODS: The tumor cells were incubated with NCX inhibitors, and the uptakes of (18)FDG and (11)C-choline were measured. Flow cytometric measurements of intracellular Ca(2+) and Na(+) concentrations were carried out. The presence of the NCX antigen in the cancer cells was proved by Western blotting, flow cytometry and confocal laser scanning microscopy. RESULTS: The NCX is expressed at a noteworthy level in the cytosol and on the cytoplasmic membrane of the examined cells. Incubation of the cells with three chemically unrelated NCX blockers (bepridil, KB-R7943 or 3',4'-dichlorobenzamil hydrochloride) resulted in an increase in the intracellular Ca(2+) concentration, with a simultaneous decrease in the intracellular Na(+) concentration. The treatment with the NCX inhibitors increased the energy consumption of the tumor cells by 50-100%. Thapsigargin abolished the NCX-induced (18)FDG accumulation in the cells. The NCX blockers applied decreased the (11)C-choline accumulation of all the investigated cancer cells by 60-80% relative to the control. CONCLUSION: A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

OBJECTIVE: Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. METHOD: Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. RESULTS AND DISCUSSION: Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. CONCLUSIONS: The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

Regional cerebral (18)FDG uptake during subarachnoid hemorrhage induced vasospasm.

OBJECTIVES: The aim was to elucidate whether aneurysmal subarachnoid hemorrhage (SAH)-induced vasospasm induces changes of regional glucose uptake in surgically treated, asymptomatic cases. METHODS: (18)FDG uptake (standardized uptake value, SUV) was analysed with PET in eight surgically treated aneurismal patients with a mean middle cerebral artery flow velocity >120 cm/seconds measured with transcranial Doppler ultrasound. Data were compared with a healthy control group using Statistical Parametric Mapping (SPM99b). RESULTS: Six of the eight patients had no focal neurological signs. The inhomogeneous bilateral increase in SUV (p<0.0001) was asymmetrical, with an almost 70% larger volume on the operated side. Reduced glucose uptake was found in the frontal and temporobasal regions of the two patients with neurological deficits (p<0.0001); the affected volume was 40% larger on the operated side. DISCUSSION: SAH-induced vasospasm results in widespread increase of glucose uptake-probably reflecting increased glycolysis. This was earlier than neurological focal signs appear. Decreased glucose uptake can be detected in severe cases of vasospasm reflected by neurological deficit. Although the changes are more prominent where surgery had taken place our results suggest that not only the surgery, but also subarachnoid blood might have resulted in our findings.

Pattern of increased cerebral FDG uptake in Down syndrome patients.

Resting cerebral glucose metabolism was assessed by 18[F]-fluorodeoxyglucose in 11 Down syndrome patients. Standardized uptake values were determined on a pixel-by-pixel basis from the measured tissue-activity data. The results revealed a mean overall 18[F]-fluorodeoxyglucose uptake in the Down syndrome patients close to that observed in the control group, consisting of children and young adults. However, the standard deviation of the standardized uptake values was much higher in the Down syndrome group in almost all voxels relating to the gray matter. The statistical parametric mapping method was applied to compare the cerebral 18[F]-fluorodeoxyglucose accumulation patterns of the Down syndrome and control groups. Six regions (clusters) were found for which the glucose uptake was higher in the Down syndrome patients than in the control group. The anatomic localization of these clusters was based on magnetic resonance investigations and a brain-atlas technique. The localization of the identified clusters with an increased glucose metabolism in the Down syndrome patients suggests that these subjects have an enhanced resting neuronal activity in cortical areas involved in reasoning, cognition, and speech as compared with normal subjects.

Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells.

AIM: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. METHODS: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. RESULTS: The (18)FDG measurements revealed that the glucose metabolic rate was significantly higher (p<0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70microM) increased the (18)FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their (11)C-choline uptake. Paclitaxel reinstated the (99m)Tc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). CONCLUSION: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images.

Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25-30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians.

Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.

The pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism in chronic ischemic stroke patients (n=13) were studied with positron emission tomography in a double-blind design. The regional and global cerebral metabolic rates of glucose (CMRglc) and cerebral blood flow (CBF) as well as vital physiological parameters, clinical performance scales, and transcranial Doppler parameters were measured before and after the treatment period in patient groups treated with daily intravenous infusion with or without vinpocetine. While the global CMRglc values did not change markedly as a result of the infusion treatment with (n=6) or without (n=7) vinpocetine, the global CBF increased and regional CMRglc and CBF values showed marked changes in several brain structures in both cases, with more accentuated changes when the infusion contained vinpocetine. In the latter case the highest rCBF changes were observed in those structures in which the highest regional uptake of labelled vinpocetine was measured in other PET studies (thalamus and caudate nucleus: increases amounting to 36% and 37%, respectively). The findings indicate that a 2-week long intravenous vinpocetine treatment can contribute effectively to the redistribution of rCBF in chronic ischemic stroke patients. The effects are most pronounced in those brain regions with the highest uptake of the drug.

Effects of miltefosine on membrane permeability and accumulation of [99mTc]-hexakis-2-methoxyisobutyl isonitrile, 2-[18F]fluoro-2-deoxy-D-glucose, daunorubucin and rhodamine123 in multidrug-resistant and sensitive cells.

Miltefosine is a phospholipid analog that exhibits antineoplastic activity against breast cancer metastases, but its mechanism of action remains uncertain. The aim of this study was to investigate the transport mechanism for the removal of miltefosine and [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) from multidrug-resistant cells. The P-glycoprotein pump function, cell viability, and 99mTc-MIBI and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) uptakes were measured in NIH 3T3 (3T3) and NIH 3T3MDR1 G185 (3T3MDR1) mouse fibroblasts and human lymphoid B JY cells. Miltefosine treatment increased the permeability and fluidity of these tumor cells in a concentration-dependent manner. The multidrug-sensitive cells were 3-4 times more sensitive to miltefosine than the multidrug-resistant ones. The extent of 99mTc-MIBI accumulation in the P-glycoprotein-expressing cells increased in the presence of miltefosine, whereas the rhodamine123 and daunorubicin uptakes of the cells did not change significantly. In the 3T3MDR1 cells verapamil reinstated the rhodamine123 and daunorubicin accumulation, but not the 99mTc-MIBI uptake. Cyclosporin A reinstated the uptakes of 99mTc-MIBI, daunorubicin and rhodamine123 by the 3T3MDR1 cells. In a concentration-dependent manner miltefosine decreased the extents of 99mTc-MIBI, rhodamine123, daunorubicin and 18FDG accumulation in the JY and 3T3 cells. Our findings indicate a common transport mechanism for 99mTc-MIBI and miltefosine, which is distinct from that for rhodamine123 and daunorubicin in MDR cells.

Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands.

AIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. METHODS: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc-MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) were measured. RESULTS: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. CONCLUSIONS: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.

Does increased 18FDG uptake reflect malignant transformation of a low-grade glioma? A diagnostic dilemma.

Benign gliomas of the brain show decreased uptake of 18F fluorodeoxyglucose (FDG) on positron emission tomography (PET). Malignant transformation is usually manifested by an increase of 18FDG uptake. A 45-year-old female has been followed up since 1987 by means of 18FDG-PET for a right hemispheric World Health Organization Grade II oligoastrocytoma. In 1996, increased epileptic activity was accompanied by increased 18FDG uptake within the temporal part of the tumor. After surgery, the epileptic seizures diminished. Histological examination of the resected tumor showed no change in the pathology when compared with the first biopsy. Localized temporal increase of 18FDG uptake was not associated with malignant progression. The decrease of seizure frequency might shed light on a putative connection of hyperglycolysis and epileptic discharges.

[Volumetric changes following 125I interstitial brachytherapy of gliomas]. / Térfogatváltozások agydaganatok 125-jód-izotópos brachytherapiája után.

BACKGROUND: Image fusion permits quantitative analysis of the consequences of 125 Iodine interstitial irradiation of brain tumors. The volume of tumor necrosis, reactive zone and edema can be compared to the dosimetric data. PATIENTS AND METHOD: Nineteen patients with low grade glioma were analyzed on the average 14.5 months following 125 Iodine interstitial irradiation. Dose planning and image fusion were performed with the Target 1.19 (BrainLab) software. The CT/MR images showing the so called "triple ring" (necrosis, reactive ring and edema) developing after the interstitial irradiation of brain tumors were fused with the planning images and the isodose curves. The volume of the three regions was measured. Values at the intersections of isodose curves and necrosis borders were averaged and used for calculation of tumor necrosis. The volume of normal brain tissue irradiated by given dose values, as well as homogeneity and conformality indices were also determined. RESULTS: The relative volumes of the different parts of the "triple-ring" compared to the reference dose volume were the following: necrosis 54.9%, reactive zone 59.7%, and edema 445.3%. Tumor necrosis developed at 71.9 Gy dose. At the irradiation of an average size glioma with a volume of 12.7 cm3, 5 to 7 cm3 normal brain tissue around the tumor received 60-70 Gy dose. The average homogeneity and conformality indices were 0.24 and 0.57, respectively. CONCLUSION: The analysis of changes in the volume of edema, reactive ring and necrosis caused by interstitial irradiation, and their correlation with the dosimetric data using the image fusion method provide useful information for patient follow-up, clinical management and further therapeutic decisions.

[The role of positron emission tomography (PET) in the detection of local recurrence and metastases of colorectal cancer]. / A pozitronemissziós tomográfia (PET) szerepe a colorectalis carcinomák lokális recidívájának és metasztázisainak felismerésében.

We presented here the results of PET imaging of 12 patients, previously operated on for colorectal cancer and followed at the 1st Department of Surgery, University of Debrecen. The tests were carried out using 0.15 mCi/kg FDG injections. Whole body imaging was performed in eleven patients. The indication for PET was elevated tumor marker levels in three patients, although CT scan was negative. The PET scan showed lymph node, hepatic and disseminated lymph node metastases with liver involvement in these patients. Suspicious lesions were found on CT scan in the pelvis of four patients. Local recurrence was identified in three of them, PET was negative in the fourth case. Bone scan suggested rib metastasis in one patient, which was not supported at PET investigation. In one patient, the malignant nature of large retroperitoneal lymph nodes could not be determined by CT. PET imaging proved that they were malignant and detected a previously unknown pulmonary metastasis at the same time. In one patient both pulmonary and liver metastases were seen on CT, whereas PET confirmed only the latter. Similarly, CT failed to identify liver metastasis detected at ultrasound, while PET proved it. Finally, a pulmonary metastasis detected on X-ray, could be confirmed by PET only. Based on our experience, we recommend PET-scanning with FDG when conventional imaging is equivocal and/or elevated tumor marker levels are present during follow-up. FDG-PET is important in the detection of local recurrence and metastases as well. It is advisable to use PET more often in the evaluation of patients with recurrent colorectal cancer in order to diagnose recurrences in earlier stages, which helps to identify patients who will benefit from surgery.

Population based ranking of frameless CT-MRI registration methods.

BACKGROUND: Clinical practice often requires simultaneous information obtained by two different imaging modalities. Registration algorithms are commonly used for this purpose. Automated procedures are very helpful in cases when the same kind of registration has to be performed on images of a high number of subjects. Radiotherapists would prefer to use the best automated method to assist therapy planning, however there are not accepted procedures for ranking the different registration algorithms. PURPOSE: We were interested in developing a method to measure the population level performance of CT-MRI registration algorithms by a parameter of values in the [0,1] interval. MATERIALS AND METHODS: Pairs of CT and MRI images were collected from 1051 subjects. Results of an automated registration were corrected manually until a radiologist and a neurosurgeon expert both accepted the result as good. This way 1051 registered MRI images were produced by the same pair of experts to be used as gold standards for the evaluation of the performance of other registration algorithms. Pearson correlation coefficient, mutual information, normalized mutual information, Kullback-Leibler divergence, L1 norm and square L2 norm (dis)similarity measures were tested for sensitivity to indicate the extent of (dis)similarity of a pair of individual mismatched images. RESULTS: The square Hellinger distance proved suitable to grade the performance of registration algorithms at population level providing the developers with a valuable tool to rank algorithms. CONCLUSIONS: The developed procedure provides an objective method to find the registration algorithm performing the best on the population level out of newly constructed or available preselected ones.

Partial breast irradiation with interstitial 60CO brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.

PURPOSE: To investigate the radiation-induced toxicity and cosmesis of brachytherapy (BT) alone in early stage breast cancer. METHODS AND MATERIALS: A total of 70 women diagnosed with Stage I or II breast carcinoma participated in a BT study at the Municipal Oncoradiological Center, Uzsoki Hospital, Budapest, Hungary, between November 1987 and June 1992. They had undergone breast-conserving surgery with an unknown surgical margin. The postoperative tumor bed irradiation was performed with interstitial (60)Co sources with an active length of 4 cm, with 10-mm center-to-center spacing arranged in a single plane. The median number of inserted sources was 5 (range, 2-8), with a linear activity of 133-137 MBq/cm at the beginning of the study. The 50 Gy delivered dose at 5 mm from the surface of the (60)Co sources was administered during 10-22 h to the virtual postoperative lumpectomy cavity (i.e., plane). For radiobiologic considerations, the clinical target volume (CTV) was calculated retrospectively with a 10-mm safety margin, resulting in a 72-cm(3) median CTV (range, 36-108 cm(3)) irradiated with a reference dose of 28 Gy. In the assessment of the skin and subcutaneous toxicity, the RTOG late radiation morbidity scoring system was applied. The radiosensitivity of the cultured fibroblasts was determined by clonogenic assay to check whether individual radiosensitivity played a role in the development and course of radiation-induced side-effects. RESULTS: The median follow-up was 12 years (range, 10-15 years). The population of the final study (34 cases) comprised all survivors with tumor-free breasts (27 cases) and patients with breasts erroneously ablated/excised for misinterpreted radiation-induced sequelae (7 patients). A total of 97% of the cohort (33/34) had grade > or =2, and 59% (20/34) had grade > or =3 radiation-induced toxicity. By the end of the follow-up, 85% of the patients experienced Grade > or =2 telangiectasis and 41% had Grade 3 telangiectasis. Eighty-eight percent had fibrosis of some form, and 35% had grade > or =3 fibrosis. Forty-one percent of the cohort displayed fat necrosis, which was always accompanied by Grade > or =3 fibrosis or telangiectasis. The cosmetic results were poor in 50% (17/34) of the patients. The radiosensitivity of the fibroblasts was increased in only 2/24 patients (8% of the investigated cases, in agreement with data published for the general population). Comparisons of our fibrosis prevalence data with those of others allowed an estimate of 0.47 h(-1) for the rate of recovery of DNA damage in the fibroblasts. CONCLUSIONS: Interstitial (60)Co BT of the breast tumor bed alone with a limited CTV (median, 72 cm(3)) and a total dose of 28 Gy is associated with a high rate (59%) of grade > or =3 radiation-induced toxicity and a high rate (50%) of poor cosmetic outcome at the end of a median follow-up of 12 years. A relatively high BT dose rate (1.3-2.8 Gy/h) applied during a short overall treatment time (10-22 h) and a possible geographic miss (close to skin implantation) might have contributed to the development of these sequelae.

18F-FDG PET detection of lymph node metastases in medullary thyroid carcinoma.

UNLABELLED: Postsurgically elevated or increasing serum calcitonin levels strongly suggest the presence of residual or recurrent medullary thyroid carcinoma (MTC). Several imaging modalities (sonography, MRI, CT, scintigraphy with different types of radiolabeled ligands, etc.) are routinely used in an attempt to localize tumorous tissue, but such efforts often fail. In the search for a more reliable method, 18F-FDG PET was applied to detect tumor tissue of residual or recurrent MTC. METHODS: Forty patients with a postoperatively elevated plasma calcitonin level were included. These patients underwent routine diagnostic imaging procedures (CT, MRI, and 131I-metaiodobenzylguanidine [MIBG] whole-body planar scintigraphy or SPECT) and 18F-FDG PET examinations. Two independent experts visually analyzed the images provided by each method to detect pathologic lesions. Lymph nodes of > or = 1 cm in short diameter that were detected by radiologic methods were considered to be pathologic. 18F-FDG accumulation with a sharp contour reported by both independent observers was similarly regarded as pathologic. RESULTS: PET detected 270 foci with a high tracer accumulation, whereas only 116 lesions were detected by MRI and 141 by CT. The numbers of such foci determined by PET, MRI, and CT were 98, 34, and 34, respectively, in the neck; 25, 5, and 6, respectively, in the supraclavicular regions; and 117, 35, and 39, respectively, in the mediastinum. 131I-MIBG scintigraphy findings were positive for only 3 patients. CONCLUSION: For MTC patients with a postoperatively elevated plasma tumor marker level, PET was more sensitive and superior in localizing tumorous lymph node involvement than were the other imaging modalities, especially in the cervical, supraclavicular, and mediastinal lymphatic regions.