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This paper investigates the role of primary plane figures, primary solids, and geometric operations in Mario Botta’s architectural works during fifty years of his career. Through the selection of three case studies, the research allows the creative process to be discretized and analyzed from a geometric-mathematical point of view.

Quantitative maps of the cerebral metabolic rate of glucose (CMRGlc) derived from 2-18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) images are useful in brain studies, but practical methods are needed to allow their use in clinical routine. This review looks at the kinetic model at the basis of absolute quantification of CMRGlc and at the main methods for measuring CMRGlc using 18F-FDG PET, also focusing on some critical steps in the procedure.

After advanced age, having a parent affected with Alzheimer's disease (AD) is the most significant risk factor for developing AD among cognitively normal (NL) individuals. Although rare genetic mutations have been identified among the early-onset forms of familial AD (EOFAD), the genetics of the more common forms of late-onset AD (LOAD) remain elusive. While some LOAD cases appear to be sporadic in nature, genetically mediated risk is evident from the familial aggregation of many LOAD cases. The patterns of transmission and biological mechanisms through which a family history of LOAD confers risk to the offspring are not known. Brain imaging studies using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) have shown that NL individuals with a maternal history of LOAD, but not with a paternal family history, express a phenotype characterised by a pattern of progressive reductions of brain glucose metabolism, similar to that in AD patients. As maternally inherited AD may be associated with as many as 20 per cent of the total LOAD population, understanding the causes and mechanisms of expression of this form of AD is of great relevance. This paper reviews known genetic mutations implicated in EOFAD and their effects on brain chemistry, structure and function; epidemiology and clinical research findings in LOAD, including in vivoimaging findings showing selective patterns of hypometabolism in maternally inherited AD; possible genetic mechanisms involved in maternal transmission of AD, including chromosome X mutations, mitochondrial DNA and imprinting; and genetic mechanisms involved in other neurological disorders with known or suspected maternal inheritance. The review concludes with a discussion of the potential role of brain imaging for identifying endophenotypes in NL individuals at risk for AD, and for directing investigation of potential susceptibility genes for AD.

The extraordinary success of imatinib in gastrointestinal stromal tumor (GIST) represents a model for molecularly targeted therapy of solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. For the optimal management of the patients treated, a multidisciplinary approach, including medical oncologists, surgeons, pathologists, and radiologists is needed. In this article, we reviewed recent advances in the clinical management of GIST patients treated with imatinib, and in the knowledge of the molecular mechanisms that are basic to imatinib effects.

Aims and Background In neuroendocrine tumors of the gastroenteropancreatic (GEP) system, radiolabeled analogs of somatostatin (SST) are useful to the surgeon in different phases of treatment: preoperatively, to identify the lesion with somatostatin receptor scintigraphy (SRS), intraoperatively for localization using a hand-held gamma probe, and postoperatively acting directly to eliminate any residual tumor cells. Additional features of these analogs that are of value in treating such GEP tumors include their antiproliferative potential, which is in the process of being verified, and, above all, their antisecretory action, so effective in symptom control. In this study the authors, based on their own experience, evaluate the effectiveness of SST analogs in treating GEP endocrine tumors.Methods Three patients with malignant GEP apudomas were studied. In case 1, an insulinoma, the patient underwent four surgical procedures for ablation of the pancreatic tumor and of hepatic and lymph node metastases in addition to local radiofrequency treatment and radiometabolic therapy. Case 2 was a carcinoid tumor of the small intestine with hepatic metastases, managed by ileal resection, local radiofrequency treatment and receptor-mediated radionuclide therapy. In case 3, a non-functioning pancreatic carcinoma with liver and lymph node metastases, the patient underwent four surgical procedures, hepatic chemoembolization, antiproliferative treatment using octreotide (OCT) and metabolic radionuclide therapy.Results In all three cases SRS proved highly sensitive in the early detection of even the smallest recurrences. There was uncertainty, however, regarding the effectiveness of therapy with radiolabeled SST analogs. Hepatic metastases from the carcinoid were completely unresponsive, but in the case of the insulinoma, the hepatic metastases showed necrosis following treatment, while lymph node metastases were unaffected. In the case of the non-functioning carcinoma, there was a correlation between treatment and a marked improvement in the patient's clinical condition, although the appearance of the lesions themselves remained unchanged. The antiproliferative effect of OCT in this case was nil.Conclusions SRS proved highly accurate in detecting recurrences during follow-up. The merits of radiometabolic therapy, on the other hand, were unclear, a finding reported elsewhere in the literature, and in the only case treated by prolonged OCT treatment, no antiproliferative action was observed. The diagnostic usefulness of SRS was thus confirmed and it appears likely that radiolabeled analogs used intraoperatively for tumor localization will prove equally of value. The effectiveness of receptor-mediated radionuclide therapy is still in the process of being verified. Based on the expectation of analogs with an universal affinity for SST receptors (sst), it is reasonable to look forward to a significant increase in the efficacy of this type of therapy.

Germ cell tumor is the most common malignancy in young men. The cure rate of these patients has tremendously increased in the cisplatin era, and recent results have indicated that the management of patients with GCT is still improving. The use of FDG-PET in the management of patients with GCT has been recently investigated. This report attempts to comprehensively review new advances and delineate the potential applications of FDG-PET in GCT.

To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOEgenotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).

Reflux nephropathy (RN) is a pathophysiological human model of reduced nephron reserve, due to loss of renal mass, but little information exists about the role of urinary endothelin-1 (uET-1) in this disease. The aim of this study was to assess the presence of uET-1-like-immunoreactivity (uET-1L) in RN patients, particularly if lateralized renal damage existed.

Acceptance of technetium-99m sestamibi as a tracer of myocardial viability is growing, particularly when nitrate-enhanced imaging is used. However, few data are available on the ability of 99mTc-sestamibi to predict the evolution of global left ventricular ejection fraction (EF). The aim of this study was to examine the ability of resting and nitrate 99mTc-sestamibi single-photon emission tomography (SPET) to predict EF changes after revascularisation in patients who have chronic coronary artery disease with left ventricular dysfunction. Using baseline resting and nitrate 99mTc-sestamibi SPET, we studied 61 patients scheduled for revascularisation because of left ventricular dysfunction. EF was estimated using two-dimensional echocardiography before and after the intervention. A post-revascularisation improvement of ≥5 EF units was defined as significant. Using a 13-segment model, 99mTc-sestamibi activity was quantified and the nitrate-induced activity changes calculated. Three different criteria for detecting viability (defined as post-revascularisation reversible dysfunction) in asynergic segments were compared: (1) resting 99mTc-sestamibi activity ≥60%; (2) nitrate 99mTc-sestamibi activity ≥65%; and (3) nitrate-induced increase >+10% or nitrate-induced increase ≤+10% and nitrate activity ≥65%. EF increased significantly in 32 patients. The number of viable asynergic segments was significantly higher in these patients than in the remaining 29 subjects, and the difference was greater (P<0.0002) using definition (3) than using either baseline (P<0.002) or nitrate activity (P<0.0005). There was a significant relationship between EF changes and number of viable asynergic segments: Spearman R=0.38, P<0.005 using baseline; Spearman R=0.39, P<0.002 using nitrate activity; and Spearman R=0.55, P<0.000005 using definition (3). According to receiver operating characteristic (ROC) curve analysis, this last criterion achieved the best results (81% sensitivity, 69% specificity and 75% accuracy), with an area under the ROC curve of 0.838; this area was significantly larger than when using either baseline (0.744, P<0.02) or nitrate activity (0.747, P<0.005). 99mTc-sestamibi SPET appears able to predict the evolution of global left ventricular EF after revascularisation, thereby confirming the value of 99mTc-sestamibi as a tracer of myocardial viability. The combination of baseline resting and nitrate imaging seems to significantly improve the diagnostic accuracy of 99mTc-sestamibi SPET for this particular purpose.

OBJECTIVES

Abstract.: The purpose of this study was to characterise the nature of the baseline perfusion defects found in patients with Behet’s disease using hexamethylpropylene amine oxime single-photon emission tomography in conjunction with acetazolamide test (Acz SPET). Eleven patients underwent both baseline and Acz SPET. Regions of interest (ROIs) were drawn on the areas with decreased perfusion (D-ROI) and, in the same section, on areas with normal perfusion (N-ROI). The ROIs were then repositioned on the corresponding section on Acz SPET. The mean ROI counts were then transformed into a perfusion index value (PIV) with reference to the global brain counts. In total we found 24 D-ROIs (17 in the cortical and 7 in subcortical grey matter). The influence of Acz infusion was selectively registered in the D-ROIs, where PIVs changed from 1.230.17 (baseline SPET) to 1.630.23 (Acz SPET) (P<0.001). No significant difference was seen in the N-ROIs (1.460.21 and 1.400.17, respectively, on baseline SPET and Acz SPET). Our results demonstrate that Acz infusion increases the regional cerebral blood flow within baseline grey matter perfusion defects. This finding suggests that baseline perfusion abnormalities could reflect a disconnection rather than local vasculitic involvement.

442 patients with breast cancer were studied by means of radiologic and scintigraphic examination of the skeleton to detect the presence of bone metastases. All the patients have been clinically followed-up for a mean periode of 22 months. The overall prevalence of bone metastases at staging was 4.5 %. Bone scan showed a higher sensitivity in detecting bone metastases (90 % vs 45 %) and a lower positive predictive value (60 % vs 75 %) with respect to X-ray examination. In the present series no asymptomatic case with bone metastases was found in limited stages (T1-T2 N0-N1). The authors suggest that the bone scan be routinely included in the staging of advanced breast cancer cases and that the use of this procedure be restricted to the symptomatic patients in the more limited stages.

The study evaluated the possibility of using serum a-amylase and tissue polypeptide antigen (TPA) as biochemical markers of radiation injury in the salivary gland of patients with thyroid carcinoma treated with iodine-131. The results demonstrated that the two molecules increased 1 day after 1311 administration and returned to near control values on the 3rd day. The increase was greater and longer lasting in those patients treated with the higher 1311 administered activity. However, when the patients were divided into groups based on recovery time, which determined patients with different radionuclide elimination rates, the increase in the two molecules was greater and more lasting in those subjects with a longer period of hospitalization. A comparison with the values obtained from patients with tumours of the head and neck treated with external radiotherapy demonstrated that after the 1st day of treatment the salivary gland received an absorbed dose which, based on a-amylase levels, ranged between 0.24 and 1.89 Gy and, based on TPA levels, between 0.28 and 2.29 Gy.

Technetium 99md,l-cyclobutylpropylene amine oxime (99mTc-CBPAO) has been developed as a brain-imaging agent for single photon emission tomography (SPET).99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPLC) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74±0.06 and 0.73±0.13 (mean ± SD), respectively. These values are not significantly different from those obtained repeating the experiment with99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) (0.72±0.15 at 5 min and 0.88 ± 0.24 at 30 min after injection). Since the rat brain uptake of99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of99mTc-CBPAO and99mTc-HMPAO were 3.04±0.57 and 4.22±0.46 (mean × 10-3 ± SD × 10-3), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared. From the analysis of these curves we suggest that99mTc-CBPAO has a higher binding effect on blood components and/or a higher degradation rate in blood than that of99mTc-HMPAO. This may account for the reduced human brain uptake. In conclusion, SPET images of99mTc-CBPAO reflect blood perfusion, and they have a good diagnostic quality. The main advantage of99mTc-CBPAO is its in vitro stability; however,99mTc-HMPAO is a superior imaging agent.

Abstract.: The significance of reverse redistribution on rest-redistribution thallium-201 myocardial scintigraphy is unclear. Previous studies suggested that reverse redistribution segments with normal resting activity include viable myocardium, whilst resting defects with further worsening correspond to scar. We evaluated whether reverse redistribution has an independent significance for the prediction of post-revascularization recovery, particularly as compared with the quantification of redistribution activity. We studied 26 coronary artery disease patients with left ventricular dysfunction, who underwent 201Tl rest-redistribution single-photon emission tomography (SPET) and echocardiography before revascularization. Viability was defined by the detection of wall motion improvement on follow-up echocardiography. 201Tl activity was considered normal if ≥80%, moderately reduced if <80% but ≥50%, and severely decreased if <50%. Reverse redistribution was defined as a defect in redistribution images with ≥10% decrease in relative 201Tl activity compared with the resting value. Reverse redistribution was detected in 33 segments (10%). Baseline dysfunction was equally observed in the reverse redistribution and in the non-reverse redistribution segments (64% vs 56%, P=0.40) and the rate of asynergic segments with post-revascularization recovery was not different between the two groups (33% vs 54%, P=0.11). The rate of functional recovery in redistribution defects without reverse redistribution was 53% in moderate and 30% in severe defects; the corresponding values for the reverse redistribution segments were 50% and 27% (all non-significant versus non-reverse redistribution segments). For the prediction of post-revascularization recovery in asynergic segments, the detection of reverse redistribution on rest-redistribution 201Tl SPET does not add any information to the quantitative analysis of redistribution activity.

Abstract. It is well known that the quantitative potential of emission computed tomography (ECT) relies on the ability to compensate for resolution, attenuation and scatter effects. Reconstruction algorithms which are able to take these effects into account are highly demanding in terms of computing resources. The reported work aimed to investigate the use of a parallel high-performance computing platform for ECT reconstruction taking into account an accurate model of the acquisition of single-photon emission tomographic (SPET) data. An iterative algorithm with an accurate model of the variable system response was ported on the MIMD (Multiple Instruction Multiple Data) parallel architecture of a 64-node Cray T3D massively parallel computer. The system was organized to make it easily accessible even from low-cost PC-based workstations through standard TCP/IP networking. A complete brain study of 30 (64×64) slices could be reconstructed from a set of 90 (64×64) projections with ten iterations of the conjugate gradients algorithm in 9 s, corresponding to an actual speed-up factor of 135. This work demonstrated the possibility of exploiting remote high-performance computing and networking resources from hospital sites by means of low-cost workstations using standard communication protocols without particular problems for routine use. The achievable speed-up factors allow the assessment of the clinical benefit of advanced reconstruction techniques which require a heavy computational burden for the compensation effects such as variable spatial resolution, scatter and attenuation. The possibility of using the same software on the same hardware platform with data acquired in different laboratories with various kinds of SPET instrumentation is appealing for software quality control and for the evaluation of the clinical impact of the reconstruction methods.

The authors report on 1,017 consecutive breast cancer cases without symptomatic metastases staged by means of chest X-ray (CXR), skeletal survey (BXR) and bone scintigraphy (BS). Occult metastases (DM) detection rate was 0.88 %: 0.29 % for lung and 0.59 % for bone DM. The detection rate was correlated with clinical stage: 0.36 % for stage I, 0.20 % for stage II, 0.26 % for stages I and II, and 2.77 % for stage III cases. The sensitivity based on DM cases prevalent or surfacing within 6 months of follow-up was 0.30 for CXR, 0.22 for BXR and 0.55 for BS; specificity was 0.99, 0.98 and 0.90, respectively. The study confirms the possibility of early detection of DM with preoperative staging, but the extremely low detection rates in stage I and II cancers do not advise such a routine procedure. The higher detection rate of DM may suggest adoption of the routine staging procedure in stage III cancers. In these cases, although no evidence is available of a favorable prognostic impact of early detection and treatment of DM, an unnecessary mastectomy could be avoided in about 3 % of cases in the presence of DM detected by the staging procedure.

This report describes a comparative study between technetium-99m ethyl cysteinate dimer (ECD) and 99mTc-hexamethylpropylene amine oxime (HMPAO) in five neurological patients. The conversion kinetics of the tracers in the blood from forms capable of diffusion across the blood-brain barrier to non-diffusible forms were studied by arterial sampling and rapid octanol extraction. We observed that HMPAO has a faster conversion rate in the blood but that the fraction of the injected dose available for brain extraction is higher than in the case of ECD. Regional brain concentrations of the tracers were measured with single-photon emission tomography (SPET) 35 min and 60 min after the injection and remained stable within this interval. On the basis of the measurements of the arterial input and of SPET brain concentrations of the tracers, the regional steadystate influx constants (Ki in ml/min/g) were determined for several brain regions. In the grey matter the Ki values were (mean ± SD) 0.32 ± 0.03 and 0.35 ± 0.04 for HMPAO and ECD, respectively; in the white matter the values were 0.23 ± 0.01 and 0.23 ± 0.02, respectively. The Ki values of the two tracers in corresponding regions were closely correlated (P<0.001). The correspondence of the Ki values of ECD and HMPAO demonstrates that ECD can also be considered a tracer that may be used for quantitative measurements of brain perfusion.

A brain phantom is described that is characterized by a high anatomical definition and by the possibility of varying the internal contrast with the use of a single radioactive solution. The experimental work was done with a single-photon emission computerized tomographic (SPET) rotating camera. The phantom was used to study the contrast recovery of both the filtered back-projection and an iterative reconstruction algorithm. Moreover, it was also used to find a cross-calibration factor between activity concentrations in the SPET slices and an external reference.

Thirty patients thyroidectomized for differentiated thyroid cancer were studied. Serum TSH was assayed in basal conditions and after TRH stimulation, while patients were in suppressive therapy with thyroid hormones. The basal TSH was normal in all the patients and less than 2 μ/ml in 20 patients. The TRH test was negative (no TSH response) in 27 patients and in all the cases with the basal TSH lower than 2 μU/ml.

This FDG-PET study with SPM99 compared 46 patients with sporadic Alzheimer disease (SAD) to 40 patients with familial AD (FAD) and to 35 matched controls. AD groups had equivalent metabolic (METglu) reductions in several cortical and limbic areas with respect to the controls. Patients with FAD showed decreased METglu in the posterior cingulate, parahippocampal, and occipital cortex as compared to the patients with SAD (p< 0.001). Genetic factors lead to phenotypic differences in AD.

Direct plating medium on cefsulodin-irgasan-novobiocin agar was as effective as 2-day enrichment in peptone-sorbitol-bile salts broth for recovery of Yersinia enterocolitica from fecal samples of patients with gastrointestinal disturbances.

The diagnostic efficacy of 99mTc-citrate brain scintigraphy was assessed in 22 patients with proven brain lesions. All patients were given 99mTc-DTPA and then 2 days later, 99mTc-citrate. Our results show a superior diagnostic efficacy of the 99mTc-DTPA test in detecting brain lesions both of vascular and neoplastic type, especially when the lesions have a poor blood supply.