Investigating the genetic characteristics of CAD: Is there a role for myocardial perfusion imaging techniques?

Several environmental and genetic factors have been found to influence the development and progression of coronary artery disease (CAD). Although the effects of the environmental hazards on CAD pathophysiology are well documented, the genetic architecture of the disease remains quite unclear. A number of single-nucleotide polymorphisms have been identified based on the results of the genome-wide association studies. However, there is a lack of strong evidence regarding molecular causality. The minority of the reported predisposing variants can be related to the conventional risk factors of CAD, while most of the polymorphisms occur in non-protein-coding regions of the DNA. However, independently of the specific underlying mechanisms, genetic information could lead to the identification of a population at higher genetic risk for the long-term development of CAD. Myocardial single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional imaging techniques that can evaluate directly myocardial perfusion, and detect vascular and/or endothelial dysfunction. Therefore, these techniques could have a role in the investigation of the underlying mechanisms associated with the identified predisposing variants, advancing our understanding regarding molecular causality. In the population at higher genetic risk, myocardial SPECT or PET could provide important evidence through the early depiction of sub-clinical dysfunctions, well before any atherosclerosis marker could be identified. Notably, SPECT and PET techniques have been already used for the investigation of the functional consequences of several CAD-related polymorphisms, as well as the response to certain treatments (statins). Furthermore, therefore, in the clinical setting, the combination of genetic evidence with the findings of myocardial SPECT, or PET, functional imaging techniques could lead to more efficient screening methods and may improve decision making with regard to the diagnostic investigation and patients' management.

Lung scintigraphy with nonspecific human immunoglobulin G ((99m)Tc-HIG) in the evaluation of pulmonary involvement in connective tissue diseases: correlation with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT).

PURPOSE: In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients. METHODS: Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs-abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained. RESULTS: Significant difference was found between HIG scores in the two groups (0.6 +/- 0.07 vs 0.51 +/- 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity. CONCLUSIONS: HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved.

Hepatobiliary scintigraphy and gamma-GT levels in the differential diagnosis of extrahepatic biliary atresia.

AIM: The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as the cause of cholestasis in neonates with prolonged jaundice and thus accelerate the decision for surgical intervention, which is critical for prognosis. METHODS: We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They were referred because of direct hyperbilirubinemia and jaundice persisting beyond the 2nd postnatal week. They had received phenobarbitone premedication prior to scintigraphy. Dynamic images for 30 min and then static images (if required) at 1, 2 and 24 h postinjection were acquired. Images were evaluated visually and semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared (Mann-Whitney U test) between infants with EHBA (Group A) and infants without (Group B). The L/H ratios were correlated with age in each group and with gamma-GT in the entire population. RESULTS: A total of 7/21 infants were classified in Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A. The correlation between L/H ratio and age was negative in EHBA and positive in non-atretic infants. The gamma-GT levels were inversely correlated with the L/H ratios in the entire population, being significantly higher in Group A. CONCLUSION: In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA scintigraphy and the L/H ratio index seem to give useful information in the differential diagnosis of EHBA, especially when associated with markedly elevated serum gamma-GT levels.

Value of thyroglobulin to 131I uptake ratio in selection of initial therapy dose of 131I in patients with differentiated thyroid carcinoma.

AIM: To test the hypothesis that the ratio of thyroglobulin (Tg) to 131I uptake in the thyroid bed during the immediate post-thyroidectomy work-up could be used before first 131I treatment to detect patients with residual or metastatic thyroid cancer and justify the administration of a higher ablation dose in selected cases and a possibly better therapeutic effect. METHODS: We retrospectively studied 293 patients with differentiated thyroid carcinoma that received their first 131I treatment in our department. Patients with Tg >100 ng/mL, 131I uptake >10% and measurable Tg-specific autoantibodies, were excluded. According to the post-therapy total body scan (TBS), we divided them in 2 groups: group I, without metastases (negative TBS), and group II, with metastases (positive TBS). The ratio of Tg to 131I uptake measured before the first 131I treatment was calculated in both groups. RESULTS: A total of 248 patients were included in the study; 225 in group I and 23 in group II. Tg to 131I uptake ratio was significantly lower in group I (mean 2.17 ng/mL/%, range 0-36), than in group II (mean 32.7 ng/mL/%, range 2.14-220), (P<0.01). The sensitivity, specificity and accuracy (using a threshold ratio 7 ng/mL/% as normal) were all 95.6% for predicting a positive post-therapy TBS. CONCLUSIONS: The use of a threshold ratio 7 ng/mL/% as the upper limit of normal provides useful information with higher sensitivity and specificity in identifying patients with metastatic disease creating the possibility for the selective use of higher initial iodine therapy doses.

Multiple meningiomas.

A 57-year-old woman with hyperthyroid ophthalmopathy underwent somatostatin receptor scintigraphy with In-111 pentetreotide. She also reported migraine-type headaches over the previous 3 months, without any other obvious neurologic symptoms and signs. The study revealed an increased uptake of the radiopharmaceutical in both periorbital areas and the right lobe of the thyroid gland. Multiple foci of marked tracer uptake were also detected in the right half of the head. A brain MRI scan subsequently revealed multiple lesions consistent with meningiomas on the surface of the right cerebral hemisphere.

Reverse of the differential uptake intensity of Tc-99m MIBI and Tc-99m V-DMSA by multiple myeloma lesions in response to therapy.

PURPOSE: The objective of this study was to compare the uptake changes of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) and Tc-99m pentavalent dimercaptosuccinic acid (V-DMSA) in multiple myeloma (MM) lesions in response to high-dose chemotherapy (HDC). MATERIALS AND METHODS: The authors compared Tc-99m MIBI and Tc-99m V-DMSA scans before and after HDC in a patient with focal MM lesions without amyloidosis who had received previous standard chemotherapy as well. RESULTS: HDC had the effect of eliminating all Tc-99m MIBI uptake in the lesions. Tc-99m V-DMSA uptake was increased in lesions presenting significant initial Tc-99m MIBI uptake. In 1 particular lesion that demonstrated this phenomenon, magnetic resonance showed necrosis of the area of MM. CONCLUSION: The authors consider that the effect of increasing Tc-99m V-DMSA uptake in the absence of an increase in viable plasma cells possibly reflects the treatment-generated inflammatory and fibrotic changes and not necessarily viable tumor tissue. Exclusive focal Tc-99m V-DMSA uptake in this clinical setting could be considered as a sign of effectively treated lesions and not a sign of deterioration.