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Abstract Background We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99mTc-methylene diphosphonate (MDP) or 99mTc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis. Methods Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a “surrogate truth” reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake. Results On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUVc) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUVc > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUVc > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUVc > 8.61 (xQ) or > 13.4 (xB). Conclusion The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

Purpose: In PSMA-ligand PET/CT imaging, standardized evaluation frameworks and image-derived parameters are increasingly used to support prostate cancer staging. Clinical applicability remains challenging wherever manual measurements of numerous suspected lesions are required. Deep learning methods are promising for automated image analysis, typically requiring extensive expert-annotated image datasets to reach sufficient accuracy. We developed a deep learning method to support image-based staging, investigating the use of training information from two radiotracers., Methods: In 173 subjects imaged with 68 Ga-PSMA-11 PET/CT, divided into development (121) and test (52) sets, we trained and evaluated a convolutional neural network to both classify sites of elevated tracer uptake as nonsuspicious or suspicious for cancer and assign them an anatomical location. We evaluated training strategies to leverage information from a larger dataset of 18 F-FDG PET/CT images and expert annotations, including transfer learning and combined training encoding the tracer type as input to the network. We assessed the agreement between the N and M stage assigned based on the network annotations and expert annotations, according to the PROMISE miTNM framework., Results: In the development set, including 18 F-FDG training data improved classification performance in four-fold cross validation. In the test set, compared to expert assessment, training with 18 F-FDG data and the development set yielded 80.4% average precision [confidence interval (CI): 71.1-87.8] for identification of suspicious uptake sites, 77% (CI: 70.0-83.4) accuracy for anatomical location classification of suspicious findings, 81% agreement for identification of regional lymph node involvement, and 77% agreement for identification of metastatic stage., Conclusion: The evaluated algorithm showed good agreement with expert assessment for identification and anatomical location classification of suspicious uptake sites in whole-body 68 Ga-PSMA-11 PET/CT. With restricted PSMA-ligand data available, the use of training examples from a different radiotracer improved performance. The investigated methods are promising for enabling efficient assessment of cancer stage and tumor burden., (© 2021. The Author(s).)

Purpose: Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ( 123 I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123 I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123 I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers' data., Methods: From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16-88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses., Results: Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and "normality" limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is - 0.015 ([- 0.019, - 0.011]) for the Flash3D database versus - 0.015 ([- 0.021, - 0.009]) for ENC-DAT. Caudate-to-putamen ratios and asymmetries were not influenced by age or gender., Conclusion: The generated 123 I-FP-CIT references values have similar age-related distribution, with no increase in variance due to comorbidities when compared to values from a multi-center study with healthy volunteers. This makes it possible for sites to build their 123 I-FP-CIT references from scans acquired during routine clinical practice.

Background: We investigated the clinical performance of a quantitative multi-modal SPECT/CT reconstruction platform for yielding radioactivity concentrations of bone imaging with 99m Tc-methylene diphosphonate (MDP) or 99m Tc-dicarboxypropane diphosphonate (DPD). The novel reconstruction incorporates CT-derived tissue information while preserving the delineation of tissue boundaries. We assessed image-based reader concordance and confidence, and determined lesion classification and SUV thresholds from ROC analysis., Methods: Seventy-two cancer patients were scanned at three US and two German clinical sites, each contributing two experienced board-certified nuclear medicine physicians as readers. We compared four variants of the reconstructed data resulting from the Flash3D (F3D) and the xSPECT Bone™ (xB) iterative reconstruction methods and presented images to the readers with and without a fused CT, resulting in four combinations. We used an all-or-none approach for inclusion, compiling results only when a reader completed all reads in a subset. After the final read, we conducted a "surrogate truth" reading, presenting all data to each reader. For any remaining discordant lesions, we conducted a consensus read. We next undertook ROC analysis to determine SUV thresholds for differentiating benign and lesional uptake., Results: On a five-point rating scale of image quality, xB was deemed better by almost two points in resolution and one point better in overall acceptance compared to F3D. The absolute agreement of the rendered decision between the nine readers was significantly higher with CT information either inside the reconstruction (xB, xBCT) or simply through image fusion (F3DCT): 0.70 (xBCT), 0.67 (F3DCT), 0.64 (xB), and 0.46 (F3D). The confidence level to characterize the lesion was significantly higher (3.03x w/o CT, 1.32x w/CT) for xB than for F3D. There was high correlation between xB and F3D scores for lesion detection and classification, but lesion detection confidence was 41% higher w/o CT, and 21% higher w/CT for xB compared to F3D. Without CT, xB had 6.6% higher sensitivity, 7.1% higher specificity, and 6.9% greater AUC compared to F3D, and similarly with CT-fusion. The overall SUV-criterion (SUV c ) of xB (12) exceeded that for xSPECT Quant™ (xQ; 9), an approach not using the tissue delineation of xB. SUV critical numbers depended on lesion volume and location. For non-joint lesions > 6 ml, the AUC for xQ and xB was 94%, with SUV c  > 9.28 (xQ) or > 9.68 (xB); for non-joint lesions ≤ 6 ml, AUCs were 81% (xQ) and 88% (xB), and SUV c  > 8.2 (xQ) or > 9.1 (xB). For joint lesions, the AUC was 80% (xQ) and 83% (xB), with SUV c  > 8.61 (xQ) or > 13.4 (xB)., Conclusion: The incorporation of high-resolution CT-based tissue delineation in SPECT reconstruction (xSPECT Bone) provides better resolution and detects smaller lesions (6 ml), and the CT component facilitates lesion characterization. Our approach increases confidence, concordance, and accuracy for readers with a wide range of experience. The xB method retained high reading accuracy, despite the unfamiliar image presentation, having greatest impact for smaller lesions, and better localization of foci relative to bone anatomy. The quantitative assessment yielded an SUV-threshold for sensitively distinguishing benign and malignant lesions. Ongoing efforts shall establish clinically usable protocols and SUV thresholds for decision-making based on quantitative SPECT.

Calculating attenuation correction for brain PET imaging rather than using CT presents opportunities for low radiation dose applications such as pediatric imaging and serial scans to monitor disease progression. Our goal is to evaluate the iterative time-of-flight based maximum-likelihood activity and attenuation correction factors estimation (MLACF) method for clinical FDG brain PET imaging. FDG PET/CT brain studies were performed in 57 patients using the Biograph mCT (Siemens) four-ring scanner. The time-of-flight PET sinograms were acquired using the standard clinical protocol consisting of a CT scan followed by 10 min of single-bed PET acquisition. Images were reconstructed using CT-based attenuation correction (CTAC) and used as a gold standard for comparison. Two methods were compared with respect to CTAC: a calculated brain attenuation correction (CBAC) and MLACF based PET reconstruction. Plane-by-plane scaling was performed for MLACF images in order to fix the variable axial scaling observed. The noise structure of the MLACF images was different compared to those obtained using CTAC and the reconstruction required a higher number of iterations to obtain comparable image quality. To analyze the pooled data, each dataset was registered to a standard template and standard regions of interest were extracted. An SUVr analysis of the brain regions of interest showed that CBAC and MLACF were each well correlated with CTAC SUVrs. A plane-by-plane error analysis indicated that there were local differences for both CBAC and MLACF images with respect to CTAC. Mean relative error in the standard regions of interest was less than 5% for both methods and the mean absolute relative errors for both methods were similar (3.4%  ±  3.1% for CBAC and 3.5%  ±  3.1% for MLACF). However, the MLACF method recovered activity adjoining the frontal sinus regions more accurately than CBAC method. The use of plane-by-plane scaling of MLACF images was found to be a crucial step in order to obtain improved activity estimates. Presence of local errors in both MLACF and CBAC based reconstructions would require the use of a normal database for clinical assessment. However, further work is required in order to assess the clinical advantage of MLACF over CBAC based method.

Brain amyloid burden may be quantitatively assessed from positron emission tomography imaging using standardised uptake value ratios. Using these ratios as an adjunct to visual image assessment has been shown to improve inter-reader reliability, however, the amyloid positivity threshold is dependent on the tracer and specific image regions used to calculate the uptake ratio. To address this problem, we propose a machine learning approach to amyloid status classification, which is independent of tracer and does not require a specific set of regions of interest. Our method extracts feature vectors from amyloid images, which are based on histograms of oriented three-dimensional gradients. We optimised our method on 133 18 F-florbetapir brain volumes, and applied it to a separate test set of 131 volumes. Using the same parameter settings, we then applied our method to 209 11 C-PiB images and 128 18 F-florbetaben images. We compared our method to classification results achieved using two other methods: standardised uptake value ratios and a machine learning method based on voxel intensities. Our method resulted in the largest mean distances between the subjects and the classification boundary, suggesting that it is less likely to make low-confidence classification decisions. Moreover, our method obtained the highest classification accuracy for all three tracers, and consistently achieved above 96% accuracy.

Objective: Dopamine transporter single-photon emission computed tomography (SPECT) with I-FP-CIT is used widely in the diagnosis of clinically uncertain parkinsonian syndromes. In terms of the evaluation of FP-CIT SPECT, some practice guidelines state that visual interpretation alone is generally sufficient in clinical patient care, whereas other guidelines consider semiquantitative analysis of striatal dopamine transporter availability mandatory. This discrepancy might be because of a relative lack of widely available display tools for FP-CIT SPECT. In this study, we evaluate a semiquantitative slab view display optimized for visual evaluation of FP-CIT SPECT that might resolve the discrepancy., Patients and Methods: The reconstructed FP-CIT SPECT image was stereotactically normalized and scaled voxel by voxel to the mean uptake in the entire brain without striata. From the resulting distribution volume ratio image, a 12-mm-thick transversal slice (slab) through the striata was displayed with a standard colour table with predefined fixed thresholds on the distribution volume ratio. Visual scoring of the semiquantitative slab view was performed twice by four independent readers in 235 unselected patients. The specific binding ratio in the caudate and putamen was computed by fully automated semiquantitative analysis with predefined standard regions of interest in template space., Results: Intrarater and inter-rater agreement of binary visual categorization as 'normal' or 'reduced' was excellent (mean Cohen's κ=0.88 and 0.83, respectively). The area under the receiver-operator characteristic curve of the specific putamen-binding ratio for differentiation between visually normal and visually reduced (majority read) was 0.96., Conclusion: Visual interpretation of FP-CIT SPECT on the basis of the semiquantitative slab view display provides excellent stability within and between readers as well as very high agreement with semiquantitative analysis. This suggests that the slab view display enables reliable visual interpretation of FP-CIT SPECT in clinical routine patient care.

Multivariate image analysis has shown potential for classification between Alzheimer's disease (AD) patients and healthy controls with a high-diagnostic performance. As image analysis of positron emission tomography (PET) and single photon emission computed tomography (SPECT) data critically depends on appropriate data preprocessing, the focus of this work is to investigate the impact of data preprocessing on the outcome of the analysis, and to identify an optimal data preprocessing method. In this work, technetium-99methylcysteinatedimer ((99m)Tc-ECD) SPECT data sets of 28 AD patients and 28 asymptomatic controls were used for the analysis. For a series of different data preprocessing methods, which includes methods for spatial normalization, smoothing, and intensity normalization, multivariate image analysis based on principal component analysis (PCA) and Fisher discriminant analysis (FDA) was applied. Bootstrap resampling was used to investigate the robustness of the analysis and the classification accuracy, depending on the data preprocessing method. Depending on the combination of preprocessing methods, significant differences regarding the classification accuracy were observed. For (99m)Tc-ECD SPECT data, the optimal data preprocessing method in terms of robustness and classification accuracy is based on affine registration, smoothing with a Gaussian of 12 mm full width half maximum, and intensity normalization based on the 25% brightest voxels within the whole-brain region.

We propose a method for accurately localizing anatomical landmarks in 3D medical volumes based on dense matching of parts-based graphical models. Our novel approach replaces population mean models by jointly leveraging weighted combinations of labeled exemplars (both spatial and appearance) to obtain personalized models for the localization of arbitrary landmarks in upper body images. We compare the method to a baseline population-mean graphical model and atlas-based deformable registration optimized for CT-CT registration, by measuring the localization accuracy of 22 anatomical landmarks in clinical 3D CT volumes, using a database of 83 lung cancer patients. The average mean localization error across all landmarks is 2.35 voxels. Our proposed method outperforms deformable registration by 73%, 93% for the most improved landmark. Compared to the baseline population-mean graphical model, the average improvement of localization accuracy is 32%; 67% for the most improved landmark.

Aim: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used., Patients, Methods: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed., Results: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions., Conclusion: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly localizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma.

Aims: To determine whether Doppler based myocardial tissue velocity imaging (TVI) or strain rate imaging (SRI) is more accurate in detecting stress-induced ischaemia during dobutamine stress echocardiography (DSE)., Methods and Results: Regional myocardial velocity, displacement, strain rate and strain patterns during DSE were investigated in 44 routine patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy defined regional ischaemia. Curves and curved-M-mode patterns were analysed and receiver-operating-characteristics of TVI and SRI parameters were compared by their area under the curve (AUC) in the receiver-operating-characteristics. In non-ischaemic segments, peak systolic velocity and strain rate increased significantly. Unlike SRI, TVI parameters had higher values in basal than in apical segments. In 47 segments of 19 segments DSE-induced ischaemia, which was proven by scintigraphy. In ischaemia, velocity and strain rate increased less. Post-systolic shortening (PSS) was always seen in SRI but not regularly in TVI. Peak systolic velocity and systolic displacement were the best TVI-parameters of stress-induced ischaemia (AUC 0.68 and 0.77, respectively.), in SRI it was the ratio of PSS and maximal segmental deformation (AUC=0.95, p < 0.0001)., Conclusion: Compared to TVI, SRI parameters showed no major apico-basal gradient and had significantly higher diagnostic accuracy, comparable to conventional reading. SRI thus appears superior to TVI for regional ischaemia detection during DSE and may be preferred to support conventional DSE reading., (Copyright 2004 Elsevier Ltd)

Ictal pleasant feelings are a rare sign of focal epilepsies. The most popular description was performed by Dostojevskij, who reported an aura by Myshken in one of his books. No convincing evidence has been published concerning the cerebral localization of ictal happiness. In this study, the findings of 11 patients with ictal pleasant feelings are described. In eight patients, the origin of the focal epileptic activity was found in the temporal lobe (most often temporal inferior basal); in three patients, frontal or parietal lobe in addition to temporal lobe involvement was found. According to our findings ictal happiness is a localizing sign pointing to the ictal involvement of temporal mesiobasal areas. Lateralization to the right temporal lobe was found in seven and to the left temporal lobe in four patients.

Temporal lobe epilepsy (TLE) is frequently associated with sympathetic over-activity. Single photon emission computed tomography (SPECT) with 123iodine-meta-iodobenzylguanidine (MIBG), a norepinephrine analogue, showed reduced tracer uptake in cardiac sympathetic nerve endings, indicating myocardial catecholamine disturbance. We investigated whether outcome of epilepsy surgery correlates with cardiac autonomic function in TLE patients. We studied 16 TLE patients before and after epilepsy surgery. We recorded heart rate (HR) and determined sympathetic and parasympathetic cardiac modulation as powers of low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) heart rate oscillations. The LF/HF-ratio was calculated as index of sympathovagal balance. Cardiac MIBG uptake was assessed with MIBG-SPECT and compared to control data. After surgery, eight patients were seizure-free and eight had persistent seizures. Sympathetic LF-power and LF/HF-ratio were higher in patients who had persistent seizures than in patients who became seizure-free. After surgery, both parameters decreased in seizure-free patients but increased in patients with persistent seizures. MIBG uptake was lower in patients than controls and even lower in the patient subgroup who had persistent seizures. In this subgroup, MIBG uptake further decreased after surgery (P<0.05). Sympathetic cardiac modulation decreased in TLE patients after successful surgery, but further increased if seizures persisted. Reduction of cardiac MIBG uptake progressed after surgery in patients with persistent seizures. Interference of epileptogenic discharges with autonomic neuronal transmission might account for sympathetic cardiac over-stimulation and reduced MIBG uptake. Both findings are possible risk factors for sudden unexplained death and might be relevant for risk stratification in epilepsy patients.

Aim: Although the fusion of images from different modalities may improve diagnostic accuracy, it is rarely used in clinical routine work due to logistic problems. Therefore we evaluated performance and time needed for fusing MRI and SPECT images using a semiautomated dedicated software. PATIENTS, MATERIAL AND METHOD: In 32 patients regional cerebral blood flow was measured using (99m)Tc ethylcystein dimer (ECD) and the three-headed SPECT camera MultiSPECT 3. MRI scans of the brain were performed using either a 0,2 T Open or a 1,5 T Sonata. Twelve of the MRI data sets were acquired using a 3D-T1w MPRAGE sequence, 20 with a 2D acquisition technique and different echo sequences. Image fusion was performed on a Syngo workstation using an entropy minimizing algorithm by an experienced user of the software. The fusion results were classified. We measured the time needed for the automated fusion procedure and in case of need that for manual realignment after automated, but insufficient fusion., Results: The mean time of the automated fusion procedure was 123 s. It was for the 2D significantly shorter than for the 3D MRI datasets. For four of the 2D data sets and two of the 3D data sets an optimal fit was reached using the automated approach. The remaining 26 data sets required manual correction. The sum of the time required for automated fusion and that needed for manual correction averaged 320 s (50-886 s)., Conclusion: The fusion of 3D MRI data sets lasted significantly longer than that of the 2D MRI data. The automated fusion tool delivered in 20% an optimal fit, in 80% manual correction was necessary. Nevertheless, each of the 32 SPECT data sets could be merged in less than 15 min with the corresponding MRI data, which seems acceptable for clinical routine use.

Transport of 99mTc labelled albumin macroaggregates (MAA) can be used as a substitute for assessing transport of spermatozoa within the female genital tract. As yet, the velocity of tubar MAA transport has not been systematically studied in a large group. Dynamic hysterosalpingoscintigraphy (HSS) was performed after intrauterine instillation of 10-20 MBq 99mTc-MAA in 88 pre-ovulatory women suffering from infertility. They had to have anatomical patency of both tubes and at least one enlarged follicle. The direction and the latency of transport were evaluated. Forty-four per cent of patients exhibited MAA transport only to the dominant follicle, 31% to both ovaries and 16% to the contralateral ovary. In 9% no transport was visible. Fifty per cent of all patients studied exhibited MAA transport to the dominant follicle within 30 s, 75% within 20 min. Transport velocity in women having bilateral or ipsilateral transport did not differ significantly. There was no significant correlation between the size of the follicle and transport velocity. We conclude that in the majority of cases MAA transport occurs within 30 s after instillation. The variation in transport time between 30 s and 20 min suggests that dynamic scintigraphy is, in principle, better suited to a refined analysis of tubar function than static HSS.

Background: Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting., Methods and Results: DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%., Conclusions: During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.

We studied the post-ganglionic cardiac sympathetic innervation in patients with chronic temporal lobe epilepsy (TLE) by means of [(123)I]metaiodobenzylguanidine-single photon computed tomography (MIBG-SPECT) and evaluated the effects of carbamazepine on cardiac sympathetic innervation. TLE is frequently associated with dysfunction of the autonomic nervous system. Autonomic dysregulation might contribute to unexplained sudden death in epilepsy. Anticonvulsive medication, particularly with carbamazepine, might also influence autonomic cardiovascular modulation. MIBG-SPECT allows the quantification of post-ganglionic cardiac sympathetic innervation, whereas measuring the variability of the heart rate provides only functional parameters of autonomic modulation. Antiepileptic drugs, especially carbamazepine (CBZ), can affect cardiovascular modulation. We determined the index of cardiac MIBG uptake (heart/mediastinum ratio) and heart rate variability (HRV) using time and frequency domain parameters of sympathetic and parasympathetic modulation in 12 women and 10 men (median age 34.5 years) with a history of TLE for 7-41 years (median 20 years). Myocardial perfusion scintigrams were examined to rule out deficiencies of MIBG uptake due to myocardial ischaemia. To assess the possible effects of CBZ on autonomic function, we compared MIBG uptake and HRV in 11 patients who had taken CBZ and 11 patients who had not taken CBZ, and in 16 healthy controls. In order to identify MIBG uptake defects due to myocardial ischaemia, all patients had a perfusion scintigram. Cardiac MIBG uptake was significantly less in the TLE patients (1.75) than in the controls (2.14; P = 0.001), but did not differ between subgroups with and without CBZ treatment. The perfusion scintigram was normal in all patients. Time domain analysis of HRV parameters suggested the predominance of parasympathetic cardiac activity in the TLE patients, but less parasympathetic modulation in the patients treated with CBZ than in those not treated with CBZ (P < 0.05), whereas frequency domain parameters showed no significant difference between the subgroups of patients or between patients and controls. MIBG-SPECT demonstrates altered post-ganglionic cardiac sympathetic innervation. This dysfunction might carry an increased risk of cardiac abnormalities.

Background: Differential diagnosis between idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA) is often difficult in early disease stages. Since MSA is misdiagnosed as PD in more than 20% of the early stages, there is need for methods refining the differentiation of the two disease entities. In PD postganglionic involvement of the autonomic nervous system (ANS) predominates whereas in MSA the ANS is mainly affected in its preganglionic structures. The functional integrity of postganglionic cardiac sympathetic neurons can be investigated using I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT)., Objectives: We investigated whether I-123-MIBG-SPECT allows to differentiate between early stages of PD and MSA in patients not yet requiring L-dopa therapy., Methods: Thirty patients (10 PD and 20 MSA patients) underwent MIBG-SPECT and evaluation of heart rate variability (HRV). Patients on any medication interfering with MIBG-accumulation were excluded from the study. Cardiac perfusion was evaluated by myocardial scintigraphy., Results: The median cardiac MIBG uptake was significantly decreased in PD as well as MSA patients compared to controls (P<0.001). However, in the PD group MIBG uptake was significantly lower than in MSA (P=0.03). Even in PD patients without clinical signs of autonomic failure, MIBG uptake was significantly lower than in MSA patients (P=0.03). Analysis of heart rate parameters did not differentiate between PD and MSA patients. The median coefficient of variation was significantly smaller in PD and MSA patients compared to control subjects., Conclusions: Our study shows that MIBG-SPECT identifies autonomic cardiac dysfunction in very early stages of both, PD and MSA. More importantly, the technique facilitates differentiation of MSA and PD in the early stages. The different pathology with prominent peripheral, postganglionic sympathetic dysfunction in PD and primarily central and preganglionic lesions in MSA accounts for a lower MIBG uptake in PD compared to MSA patients.

We investigated cardiac sympathetic innervation by metaiodobenzylguanidine (MIBG) imaging in a patient with tonic pupils, loss of tendon reflexes, and segmental anhidrosis (Ross syndrome). Despite normal cardiovascular reflex tests, we observed a reduced global myocardial MIBG uptake as well as a regional uptake defect over the posterolateral cardiac territory indicating left ventricular peripheral sympathetic denervation. MIBG imaging seems to be a useful noninvasive diagnostic method for detection of early--possibly subclinical--cardiac autonomic impairment in Ross syndrome and provides further evidence of injury to postganglionic autonomic neurons as the underlying pathological mechanism of the disease.

Involvement of the autonomic cardiac nervous system in early stages of amyotrophic lateral sclerosis (ALS) was evaluated in 40 patients. I-123-metaiodobenzylguanidine-single photon emission computed tomography (MIBG-SPECT) and heart rate variability (HRV) yielded information about sympathetic and parasympathetic innervation of the heart. MIBG-SPECT is a sensitive diagnostic method for demonstration of early cardiac sympathetic denervation. Both sympathetic and parasympathetic dysfunction was observed in 16 (40%) out of 40 patients. Mean cardiac MIBG uptake as demonstrated by the heart/mediastinum ratio was significantly reduced in all ALS patients in comparison with controls (P<0.01). The global MIBG-SPECT score was clearly abnormal in 29% and slightly abnormal in 22% of patients. HRV was diminished in 6 of 38 patients, 4 of whom having an abnormal MIBG-SPECT score as well. The presented results indicate that ALS patients with mild to moderate impairment may have evidence of postganglionic sympathetic adrenergic cardiac or cardiovagal denervation. To our knowledge, this is the first study indicating possible postganglionic sympathetic denervation in ALS. The original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease which possibly represents different entities.

We report 3 cases of an ictal sinus arrest. All patients suffered from temporal lobe epilepsy (TLE). Seizures were monitored with simultaneous video-eeg during preoperative epilepsy diagnosis. One patient with cortical dysplasia, who frequently suffered from long lasting syncopes, had a nearly completely missing cardiac sympathetic innervation in MIBG-SPECT (=Meta-Iodide-Benzyle-Guanidine-single-photon-emission tomography). Cardiac investigation including long-term ECG and echocardiography had shown normal findings. After epilepsy surgery the syncopal events in all patients disappeared. A dominant parasympathetic ictal stimulus following excitation of the reticular formation might cause the ictal bradycardia and sinus arrest. A missing sympathetic innervation, possibly occurring as fehlbildung together with cortical dysplasia, which makes autoregulation impossible, might then be the explanation for sudden cardiac ictal death.

Aim: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery., Methods: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts., Results: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up., Conclusion: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and color-coded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.g. motoric or sensible defects); 6 had mild symptoms like headache or cognitive disorders, so-called minor symptoms: 16 patients did not present with any of these symptoms. SPECT abnormalities were detected in 16 of the 18 patients with overt neuropsychiatric symptoms (89%). Five of the 6 patients with minor symptoms (83%) and 5 of the 16 patients without neurological symptoms (31%) also had SPECT abnormalities. There was no relation to disease activity or duration. We concluded that the high sensitivity of SPECT (87.5%) in detecting perfusion abnormalities among the evaluated group of patients indicates its suitability for early diagnosis of vasculitic CNS involvement.

In diabetic neuropathy disturbed autonomic cardiac innervation is associated with shortened life expectancy. Sympathetic dysfunction is likely to play a role in cases of cardiac death. The quantitative uptake of the radiopharmaceutical iodine-123-meta-iodo-benzylguanidine (MIBG) can be measured by single photon emission computed tomography (SPECT). It is an index of the functional integrity of sympathetic neurones in the heart. The respiratory heart rate variation--as assessed by a computerized device--reflects mainly parasympathetic cardiac innervation. In 25 diabetic patients and 19 healthy subjects MIBG-SPECT and heart rate variation tests were carried out. MIBG scans in all normal subjects showed homogeneous uptake of activity. In 12 out of 25 patients at least two heart rate variation tests were abnormal. MIBG-SPECT was more sensitive (abnormal in 17 out of 25). The lack of correlation between MIBG-SPECT results and spectral analysis of heart rate variation suggest that spectral analysis alone should not be regarded as an indicator of sympathetic cardiac innervation.

On the assumption that maximum R peak time prolongation in the left-sided leads I, V5, or V6 and its time relationship to the S peak time of the maximum S amplitude in leads V1, V2, or V3 (representing dorsally directed forces of ventricular depolarization) could indicate the extent of left ventricular volume overloading and possibly left ventricular systolic function, these variables and the preoperative findings of angiocardiography were compared between patients with chronic mitral incompetence who, late after corrective valve surgery, had either well-preserved radionuclide left ventricular ejection fraction (group 1, n = 36) or radionuclide left ventricular ejection fraction below 50% (group 2, n = 30). Before surgery, group 2 patients had a highly significant lower mean left ventricular ejection fraction, a highly significant greater mean end-systolic volume index, a significantly greater mean end-diastolic volume index, a significantly greater mean maximum R peak time in leads I, V5, or V6, and a significantly greater prolongation of the maximum R peak time above the S peak time in the right precordial leads, as compared with group 1. R peak times greater than 50 ms or the presence of R peak delay (maximum R peak time greater than the S peak time of the maximum right precordial S amplitude) yields less sensitive but highly reliable results in predicting radionuclide left ventricular ejection fraction below 50% with both specificity and positive predictive values of 100%. Thus, in chronic mitral regurgitation surgery should not be delayed if patients present these signs because they are specific markers of irreversibly impaired chamber function.

In order to define which of selected ECG variables could indicate irreversibly impaired myocardial function in chronic aortic regurgitation 54 patients were stratified according to normal (> or = 50%; Group A, n = 41) or subnormal radionuclide left ventricular ejection fraction (LVEF < 50%; Group B, n = 13) late after aortic valve replacement. Preoperatively, Group B patients had a significantly greater QRS duration, greater R-peak time (RPT) prolongation in I, V5 or V6, greater RPT relative to the S-peak time of the maximum S in V1, V2 or V3 (R-peak delay) and a greater negative T-wave in I or V6, as compared with Group A. These ECG variables together with preoperative angiocardiographic LVEF and end-systolic volume index were subjected to stepwise linear discriminant analysis. The maximum RPT, angio-LVEF and the maximum RPT relative to the S-peak time of the maximum S in V1, V2 or V3 emerged as the most promising variables. Of of Group A patients 82.9% and 84.6% of Group B patients were correctly classified by the three variables. If applied separately, APT prolongation or the presence of the R-peak delay in the left-sided leads, although less sensitive, have reasonably high specificity as risk indicators of irreversibly impaired chamber function, their positive predictive value being 60 and 62.5%, respectively. In conjunction with preoperative LVEF the diagnostic contribution of the two ECG variables amounts to the greatest overall separation of postoperatively preserved from irreversibly impaired systolic function.

Ictal and interictal SPECT measurements using 99mTc-HMPAO are helpful in localising an epileptic focus. 24 patients (12 women and 12 men; mean age 30 years) suffering from temporal lobe epilepsies with unilateral EEG foci were examined. In all patients a presurgical evaluation including sphenoidal and foramen oval electrodes was carried out. The analysis of SPECT measurement was done visually and semi-quantitatively, comparing the data with findings in healthy persons (10 women and 10 men; mean age 24 years). The etiology of the epilepsy was confirmed by histological investigation in 16 cases, and by CT and MRI in 8 cases. The findings were gliosis in 6 cases, astrocytoma in 3 cases, cysts in 4 cases, and angioma in 3 cases. In 8 cases no pathological findings could be detected. In 46% of cases interictal SPECTs exhibited a focal hypoperfusion corresponding with the EEG-focus. In ictal SPECTs this could be found in 75% of cases. In all 10 patients without morphological findings or with gliosis (proved by histological investigations) a hyperperfusion coincident with the EEG-focus appeared in ictal SPECTs.