Massimo Castellani

Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: Results from a randomized controlled trial

Objective Large acute ST-elevation myocardial infarction (STEMI) sometimes leaves extensive ischemic damage despite timely and successful primary angioplasty. This clinical picture of good recanalization with incomplete reperfusion represents a good model to assess the reparative potential of locally administered cell therapy. Thus, we conducted a randomized controlled trial aimed at evaluating the effect of intracoronary administration of CD133+ stem cells on myocardial blood flow and function in this setting. Methods Fifteen patients with large anterior STEMI, myocardial blush grade 0–1 and more than 50% ST-elevation recovery after optimal coronary recanalization (TIMI 3 flow) with stenting were randomly assigned to receive CD133+ cells from either bone marrow (group A) or peripheral blood (group B), or to stay on drug therapy alone (group C). The cells were intracoronary injected within 10–14 days of STEMI. Infarct-related myocardial blood flow (MBF) was evaluated by NH3 positron emission tomography 2–5 days before cell administration and after 1 year. Results MBF increased in the infarct area from 0.419 (0.390–0.623) to 0.544 (0.371–0.729) ml/min per g in group A, decreased from 0.547 (0.505–0.683) to 0.295 (0.237–0.472) ml/min per g in group B and only slightly changed from 0.554 (0.413–0.662) to 0.491 (0.453–0.717) ml/min per g in group C (A vs. C: P = 0.023; B vs. C: P = 0.066). Left ventricular volume tended to increase more in groups B and C than in group A, ejection fraction and wall motion score index remained stable in the three groups. Conclusion These findings support the hypothesis that intracoronary administration of bone marrow-derived, but not peripheral blood-derived CD133+ cells 10–14 days after STEMI may improve long-term perfusion.

The Role of PET with 13N-Ammonia and 18F-FDG in the Assessment of Myocardial Perfusion and Metabolism in Patients with Recent AMI and Intracoronary Stem Cell Injection

Over the last decade, the effects of stem cell therapy on cardiac repair after acute myocardial infarction (AMI) have been investigated with different imaging techniques. We evaluated a new imaging approach using 13N-ammonia and 18F-FDG PET for a combined analysis of cardiac perfusion, metabolism, and function in patients treated with intracoronary injection of endothelial progenitors or with conventional therapy for AMI. Methods: A total of 15 patients were randomly assigned to 3 groups based on different treatments (group A: bone marrow–derived stem cells; group B: peripheral blood–derived stem cells; group C: standard therapy alone). The number of scarred and viable segments, along with the infarct size and the extent of the viable area, were determined on a 9-segment 13N-ammonia/18F-FDG PET polar map. Myocardial blood flow (MBF) was calculated for each segment on the ammonia polar map, whereas a global evaluation of left ventricular function was obtained by estimating left ventricular ejection fraction (LVEF) and end-diastolic volume, both derived from electrocardiography-gated 18F-FDG images. Both intragroup and intergroup comparative analyses of the mean values of each parameter were performed at baseline and 3, 6, and 12 mo after AMI. During follow-up, major cardiac events were also registered. Results: A significant decrease (P < 0.05) in the number of scarred segments and infarct size was observed in group A, along with an increase in MBF (P < 0.05) and a mild improvement in cardiac function. Lack of infarct size shrinkage in group B was associated with a marked impairment of MBF (P = 0.01) and cardiac dysfunction. Ambiguous changes in infarct size, MBF, and LVEF were found in group C. No differences in number of viable segments or in extent of viable area were found among the groups. At clinical follow-up, no major cardiac events occurred in group A patients, whereas 2 patients of group B experienced in-stent occlusion and one patient of group C received a transplant for heart failure. Conclusion: Our data suggest that a single nuclear imaging technique accurately analyzes changes in myocardial perfusion and metabolism occurring after stem cell transplantation.

Relationship between serum thyroglobulin and 18FDG-PET/CT in 131I-negative differentiated thyroid carcinomas.

The purpose of this study was to assess the relationship between [18F]‐fluorodeoxyglucose (18FDG)‐positron emission tomography/CT (18FDG‐PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated thyroid carcinoma (DTC).

Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decision-making process in primary hyperparathyroid disease

Purpose Ultrasound (US) and scintigraphy are used most frequently of all the available imaging techniques for the preoperative evaluation of patients with possible primary hyperparathyroid disease. The aim of this study was to assess the value of dual-phase Tc-99m MIBI scintigraphy compared with US in the detection of adenomatous or hyperplastic glands and in the surgical decision-making process for patients with a biochemical diagnosis of primary hyperparathyroid disease. Methods Ninety-seven patients with increased levels of parathyroid hormone and calcium, and at least 6 months’ follow-up after US and scintigraphy, were examined retrospectively to assess the influence of the diagnostic work-up on the therapeutic decision of the referring clinicians and to evaluate the sensitivity of these diagnostic tools in the surgically treated patients. Forty-eight patients underwent surgery. Results Parathyroid adenomas were found in 43 patients and hyperplasia in 1, whereas 4 patients had no evidence at surgery. The sensitivity and specificity rates were 84.4% and 95.9% for scintigraphy, and 66.6% and 98.6% for US, respectively. Of the 49 nonsurgically treated patients, 35 had negative results with both MIBI and US; only 3 had positive findings with both imaging methods. Patients treated conservatively had significantly lower parathyroid hormone and serum calcium levels than did the patients who had surgery. Conclusions The data suggest that the high sensitivity of dual-phase MIBI scintigraphy can improve the detection of hyperfunctioning parathyroid glands. Furthermore, despite the controversy surrounding the use of imaging methods in the preoperative assessment of primary hyperparathyroid disease, these data suggest that the decision of the clinician to order surgery for a patient with a moderate increase of serum PTH level may be influenced by the results of the imaging methods.

The prognostic value of F-18 fluorodeoxyglucose bone marrow uptake in patients with recent diagnosis of multiple myeloma: A comparative study with Tc-99m sestamibi

Purpose: We assessed the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow of patients with multiple myeloma (MM) in comparison with Tc-99m methoxy-isobutyl-isonitrile (MIBI). Methods: The extent and intensity of FDG and MIBI uptake in the bone marrow of 18 patients with a recent diagnosis of MM were assessed by visual score and by calculating the mean SUV (mSUV) for FDG and the femora/thigh ratio (TG/BKG, [Target/Background ratio]) for MIBI images. These parameters were correlated with clinical indexes of disease using hemoglobin and beta-2-microglobulin levels and plasma cell infiltrate (PCI) percentage. The mean values of the visual score, mSUV, and TG/BKG levels were compared in patients deceased after a relatively short follow-up (n = 9; group A) and in patients with a longer survival or were alive at the end of the study (n = 9; group B). Results: Significant correlations of mSUV and TG/BKG values with PCI percentages and beta-2-microglobulin were found (P < 0.05). The extent of FDG and MIBI bone marrow uptake was greater in patients of group A (P < 0.01). Higher values of mSUV (P < 0.01) and TG/BKG (P < 0.05) were also observed in patients of group A. These results were consistent with the differences (not statistically significant) in hemoglobin, albumin, beta-2-microglobulin levels, and PCI percentages observed in the 2 groups. Conclusion: Our study demonstrates that an increase of FDG bone marrow uptake may predict a more aggressive disease, as much as MIBI uptake. Therefore, an additional analysis of FDG bone marrow images should be performed in patients undergoing PET studies during the initial staging of MM.

Case report: technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile imaging of breast cancer and myocardial infarction in the same patient.

Technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (MIB!) is a lipophilic cation widely employed in clinical practice as a myocardial perfusion imaging agent (13, 14). Recent investigations have demonstrated that MIBI passes cell and mitochondrial walls because of negative transmembrane potentials (3, 11). Moreover, intracellular MIBI uptake is increased in carcinoma cell lines due to a higher metabolic activity (4). Several studies have proposed MIBI as an oncologic tracer for a variety of malignancies, including tumors of the lung, thyroid, brain and bone (1, 2, 5, 7-10, 12). Recently, MIBI has been tested for its potential in breast cancer imaging (6). We present a case of breast cancer occasionally imaged with MIBI single photon emission tomography (SPET) in a patient under examination for electrocardiographic (ECG) signs of myocardial necrosis of the inferolateral wall.

Multi-field-of-view SPECT is superior to whole-body scanning for assessing metastatic bone disease in patients with prostate cancer.

AIM The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (PCa). METHODS In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed PCa and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. RESULTS The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. CONCLUSION Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in PCa patients.

Indium-111 pentetreotide lung uptake in infectious lung disease.

Bilateral diffuse lung uptake of In-111 pentetreotide (OCT) was observed during a whole-body scan performed in a 68-year-old woman with Cushings syndrome and suspected ectopic adrenocorticotropic hormone secretion. A few days later, she was found to have bilateral bacterial pneumonia (of mixed anaerobic origin). Cushings syndrome was finally proved to be of pituitary origin. The OCT lung uptake in pneumonia probably resulted from tracer binding by somatostatin receptors on the inflammatory leukocytes. Although the rapid wash-out from experimentally induced abscesses does not make OCT a suitable tracer for detecting acute infections, the images and data here reported suggest that infectious lung disease should be excluded before diagnosing lung involvement by neuroendocrine tumors.

Background based Gaussian mixture model lesion segmentation in PET

PURPOSE Quantitative (18)F-fluorodeoxyglucose positron emission tomography is limited by the uncertainty in lesion delineation due to poor SNR, low resolution, and partial volume effects, subsequently impacting oncological assessment, treatment planning, and follow-up. The present work develops and validates a segmentation algorithm based on statistical clustering. The introduction of constraints based on background features and contiguity priors is expected to improve robustness vs clinical image characteristics such as lesion dimension, noise, and contrast level. METHODS An eight-class Gaussian mixture model (GMM) clustering algorithm was modified by constraining the mean and variance parameters of four background classes according to the previous analysis of a lesion-free background volume of interest (background modeling). Hence, expectation maximization operated only on the four classes dedicated to lesion detection. To favor the segmentation of connected objects, a further variant was introduced by inserting priors relevant to the classification of neighbors. The algorithm was applied to simulated datasets and acquired phantom data. Feasibility and robustness toward initialization were assessed on a clinical dataset manually contoured by two expert clinicians. Comparisons were performed with respect to a standard eight-class GMM algorithm and to four different state-of-the-art methods in terms of volume error (VE), Dice index, classification error (CE), and Hausdorff distance (HD). RESULTS The proposed GMM segmentation with background modeling outperformed standard GMM and all the other tested methods. Medians of accuracy indexes were VE <3%, Dice >0.88, CE <0.25, and HD <1.2 in simulations; VE <23%, Dice >0.74, CE <0.43, and HD <1.77 in phantom data. Robustness toward image statistic changes (±15%) was shown by the low index changes: <26% for VE, <17% for Dice, and <15% for CE. Finally, robustness toward the user-dependent volume initialization was demonstrated. The inclusion of the spatial prior improved segmentation accuracy only for lesions surrounded by heterogeneous background: in the relevant simulation subset, the median VE significantly decreased from 13% to 7%. Results on clinical data were found in accordance with simulations, with absolute VE <7%, Dice >0.85, CE <0.30, and HD <0.81. CONCLUSIONS The sole introduction of constraints based on background modeling outperformed standard GMM and the other tested algorithms. Insertion of a spatial prior improved the accuracy for realistic cases of objects in heterogeneous backgrounds. Moreover, robustness against initialization supports the applicability in a clinical setting. In conclusion, application-driven constraints can generally improve the capabilities of GMM and statistical clustering algorithms.

Thyroid remnant estimation by Tc-99m-sestamibi scanning predicts the effectiveness of rhTSH-stimulated I-131 ablation in patients with differentiated thyroid carcinoma

Aim: To evaluate the relationship between postsurgical cervical Tc-99m-sestamibi scan uptake and the rate of successful remnant ablation after recombinant human-thyrotropin (rhTSH)-aided-I-131 ablation in patients with differentiated thyroid carcinoma (DTC). Methods: In all, 154 DTC patients who underwent total thyroidectomy and rhTSH-aided remnant ablation with I-131 (3.7 GBq) were enrolled. Tc-99m-sestamibi scans were performed during continuing thyroid hormone administration in all cases. Thyroid ablation was assessed after 6 to 12 months by rhTSH-stimulated I-131-whole-body scan and thyroglobulin measurement. The rate of successful ablation, occurrence of radioiodine-induced thyroiditis, and length of hospitalization were correlated with the Tc-99m-sestamibi scintigraphy results. Results: Tc-99m-sestamibi uptake was significantly lower in ablated versus nonablated patients (P < 0.0001). A visually positive scan and a Tc-99m-sestamibi uptake greater than 0.9% predicted a high-risk of unsuccessful ablation, prolonged hospitalization, and the occurrence of radioiodine-induced thyroiditis. Conclusions: Tc-99m-sestamibi scintigraphy is a simple and feasible tool to evaluate thyroid remnants and to predict radioiodine ablation results in patients with DTC.