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We distinguished the scintigraphy pattern of congenital reflux nephropathy from that of acquired scarring in children with primary vesicoureteral reflux.We retrospectively evaluated the frequency and pattern of renal scintigraphy abnormalities in 41 patients with prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the infection was cured in patients with urinary tract infection and prenatal detection, respectively.We identified 3 patterns of renal damage, including overall decreased uptake of renal radionuclide that was 20% to 40% of relative uptake, focal defects in uptake and shrunken kidney with relative uptake less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken kidney in 42%, and in 111 cases of reflux detected at urinary tract infection, including overall decreased uptake in 50%, uptake focal defects in 37% and shrunken kidney in 13%. In the urinary tract infection group overall decreased uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these children 15% of the girls had uptake focal defects and 17% had overall decreased uptake. Overall decreased uptake and uptake focal defects were significantly more common in kidney-ureter units with reflux grade 4 or greater than in those with grade 3 or less (p = 0. 00001 and 0.027, respectively).When assuming that overall decreased radionuclide uptake indicates congenital reflux nephropathy and uptake focal defects indicate postnatal acquired scarring, congenital reflux nephropathy appears to be an important cause of renal damage in children with primary vesicoureteral reflux even beyond the neonatal age and even in girls. This finding is of interest because postnatally acquired scarring may but congenital reflux nephropathy may not be prevented.

We compared the accuracy of isotope cystography (IC) and fluoroscopic cystourethrography (FC) in detecting vesicoureteric reflux (VUR) in children. FC and IC were performed in 124 children, 56 boys and 68 girls, aged 1 month to 9.2 years (mean 2.1 years), admitted consecutively for suspected VUR over a 10-month period. VUR was diagnosed by one or both studies in 51 of 124 (41%) patients. The two methods were concordant for the detection of VUR in 84% of kidney-ureter units and in 93% for the detection or exclusion of severe VUR. IC detected VUR more accurately than FC, both when all grades of VUR were considered together (P=0.00001) and when only severe reflux was considered (P=0.004). VUR was missed by FC in 23 of 51 (45%) subjects. Of those 23, 12 had severe VUR detected on one side at least by IC. VUR was missed by IC in 3 subjects. IC is significantly more accurate than FC in the initial diagnosis of VUR, even of severe grade. IC is the method of choice for the first diagnosis of VUR. Boys with VUR diagnosed by IC also need FC to investigate for posterior urethral valves.

OBJECTIVES The aim of this study was to evaluate: 1) the effects of insulin administration on left ventricular ejection fraction (LVEF) during exercise, and 2) the eventual impairment of the cardiovascular response to insulin in noninsulin dependent diabetes mellitus. BACKGROUND Insulin influences the cardiovascular system, but its effect on left ventricular function has yet to be established. METHODS The effects of normal saline (test A) and insulin-glucose (insulin = 1.7 mU·kg−1·min−1; glucose = 6 mg·kg−1·min−1) (test B) infusions on systolic and diastolic functions at rest and during dynamic exercise were examined by radionuclide ventriculography. Twenty-two noninsulin-dependent diabetic patients and 22 gender, age and body mass index matched healthy subjects were investigated. RESULTS Both groups had normal scintigraphic parameters at rest and during dynamic exercise. Rest- and stress-LVEF as well as rest- and stress-peak filling rate were significantly (p CONCLUSIONS In both normal and diabetic humans, insulin induces a very important rise in LVEF after submaximal work. However, the rise is significantly lower in diabetic than in nondiabetic subjects. The increase in exercise-LVEF on insulin is likely due to an enhancement of ventricular contractility. Insulin resistance could justify the lower angioscintigraphic indexes in diabetic subjects.

A combined surgical procedure, left ventricular restoration (LVR), consisting of coronary artery bypass graft and endoventricular patch plasty (EPP), is under investigation in on-going STICH trial (1). EPP may provide restoration of left ventricular (LV) size and geometry by excluding nonviable areas. At present, the differentiation of viable tissue and scar is based on subjective methods, assessing morphological features such as consistency, thickness and color of the wall, and it may be inadequate on surgery table. We assessed the feasibility of in vivo radioguided surgery (RGS) by a gamma-probe as an objective tool to differentiate viable tissue and scar in patients undergoing EPP.

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min × 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR 2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

Among radionuclides usable for tumor therapy, α-particle emitters are characterized by a very high linear energy transfer (LET) resulting in a larger number of ionizations in a range corresponding to a cell diameter. Therefore, they can determine a stronger therapeutic effect compared to low LET β-particle emitters, producing their ionizations in a range up to many millimeters. In fact, because the distance between the two strands of DNA is almost the same as the distance between two ionizations of α-particles, DNA double strand breaks are induced with a high probability that finally cause cell death due to inefficient repair. Conversely, no therapeutic effect can be determined outside of concentrating sites. Therefore, the short range of α-emitters makes them powerful tools mainly when a therapeutic effect has to be reached in a restricted area, as in the elimination of minimal residual disease or in micro-metastases. Therapeutic efficacy of α-emitter radionuclides has been proven in numerous pre-clinical studies, but up to today only three main human studies are reported, including the treatment of myeloid leukemia by an anti-CD33 monoclonal antibody labelled by bismuth- 213 (213Bi), the therapy of patients with bone metastases from hormone-refractory prostate cancer by radium-223 (223Ra) and the loco-regional targeted radiotherapy with astatine-211(211At)-labelled anti-tenascin monoclonal antibody in patients with recurrent malignant brain tumours. The authors reviewed these human reported studies, evaluating perspectives, advantages and limitations of the targeted α-particle therapy.

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This open-label, uncontrolled, retrospective study assessed the long-term effects of late thrombolysis on left ventricular (LV) function. We studied 79 patients (52 men and 27 women; mean age, 51 ± 5 years) treated with alteplase (group 1) and 46 patients (33 men and 13 women; mean age, 52 ± 8 years) treated with heparin alone (group 2) at their first myocardial infarction (MI). Patients were eligible for the study if they were younger than 62 years, their duration of pain was longer than 6 hours, and they had no episodes of angina in the 48 hours preceding their MI. The peak of creatine kinase-muscle and brain subunits was significantly less in group 1 than group 2 (106 ± 67 vs 205 ± 102 IU/L). Both LV ejection fraction and wall-motion score were better in thrombolysed patients, and the cumulative frequency of radionuclide defects was higher in these patients during the 4-year follow-up. Our study supports the concept that thrombolysis reduces the incidence of long-term post-MI residual ischemia, improving global LV function even when given late after the onset of MI symptoms.

This text is a guide to cardiovascular use of optical coherence tomography (OCT). The editor is Ik-Kyung Jang, Professor of Medicine, Harvard Medical School. He has pioneered the application of OCT in cardiology, establishing the OCTcriteria for plaque characterization and comparing OCT and intravascular ultrasonography in living patients. The book contains 15 chapters with a useful index, occupying 222 pages and including numerous representative illustrations. The first two chapters focus on the development of OCT with emphasis on fundamental notions, the process of technology translation and clinical applications, the first of which was in ophthalmology, where it has become a standard of care, and then more recently in cardiology, both as a diagnostic modality and research tool. The following chapters are devoted to OCT validation, comparing OCT images and histological findings of atherosclerotic plaque, calcification, fibroatheroma, thrombus and neointima formation, image interpretation and possible pitfalls and artifacts. However, the most interesting part centres on the clinical presentations of cardiovascular diseases, covering acute coronary syndrome and spontaneous coronary artery dissection, and on evaluation of early and late stents with regard to possible mechanisms of failure, such as malapposition, stent thrombosis and neoatherosclerosis. In chapter XIV, the authors review the conclusion of consensus documents released and highlight the importance of reaching agreement on the best OCT definitions to describe plaque anatomy and stented segments because researchers still use different criteria and descriptions. The last chapter focuses on future developments. Multimodal imaging is certainly a promising research field: the combinations of different modalities can provide unique information, overcoming the weaknesses of each technique alone. Although this volume is mainly addressed to interventional cardiologists, providing background and useful hints, we recommend this fascinating book to all clinicians interested in vascular biology to improve their understanding of the role and evolution of high-risk plaque in the pathogenesis of acute coronary syndrome.

To test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co-registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra-class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi-quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t-test, P0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P = 0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes.

Somastostatin (SS) scintigraphy (SRS) is an effective diagnostic tool for neuroendocrine tumours (NET). High diagnostic accuracy is based on the high affinity binding between SS and its receptors (sstr) expressed both in NET and in some non neoplastic cells. Different SS analogues have been proposed in clinical practice because of the short half-life of the native peptide. Among all synthetic compounds Pentetreotide labelled with In-111 is the most widely used for imaging because of high affinity for sstr 2 and 5. New tracers, showing a different and/or wider affinity, are now available and radio- labelling has been obtained both with gamma and positron emitters. The broader spectrum of interaction with sstr gives a better chance to detect, over NET, other pathological conditions, as chronic inflammation, because of the sstr expression on inflammatory cells, including activated lymphocytes, epithelioid and monocytes.

The 20th century diagnostic imaging scenario almost for the whole of its existence was divided into two well-separated universes: (1) the morphostructural, in which information on anatomy and structures are acquired, with pathology as the gold standard, and (2) the functional, in which normal and altered functions are analysed, with pathophysiology as the reference. Morphostructural techniques show differences in density, as observed in a picture taken in a steady state as a freezeframe effectively not allowing distinction between a living and a dead body. Functional techniques, which can only be applied in a living being, show dynamic changes as in a movie where “time” is a major element, taking information from parameters such as differences in concentration and movement. This category includes techniques such as urography and cardio-CT, in which increasing doses in dynamic scans and the number of acquisitions are important considerations [1]. To avoid a high radiation dose, the lowest number of frames are acquired, and this is a major disadvantage with respect to nuclear medicine and MRI, which are queens in “clinical” functional imaging because of their superiority in studying pathophysiology. Nuclear medicine as molecular imaging

Targeted alpha therapy (TAT) is an investigational procedure which utilises monoclonal antibodies (mAbs), peptide conjugates and/or other chemical compounds. These bio-vectors are able to transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labelled with beta emitters, have already been used in humans. More recently, TAT has been introduced to treat oncological diseases mainly leukaemia and lymphoma. Encouraging results have also been obtained in solid neoplasms with the administration of anti-tenascin. This chimeric antibody labelled with astatine-211 was delivered in patients with recurrent brain tumours into a surgically created cavity. Conversely, a clinical trial using a standard TAT approach to treat patients with metastatic melanoma, observed the shrinkage of the solid tumour mass. This response in melanoma may lead to an alternative mechanism for TAT, called tumour-antivascular- alpha-therapy (TAVAT), and forms the basis of a novel approach to the treatment of cancer disease states. In this paper, we will concentrate mainly on the application of TAT using antibodies. In particular, an investigation into the major general features connected with the use of alpha emitters in cancer therapy will be discussed. The prospective role of TAT with RACs will also be outlined briefly, especially focussing on the most important therapeutic strategies to date based on antibodies radiolabelled with beta emitters.

Inflammatory bowel diseases (IBD) are a group of pathological conditions characterized by chronic inflammation of the gastrointestinal tract, including Crohn's disease and ulcerative colitis. To date, imaging of IBD is based on several radiological techniques such as barium studies, magnetic resonance imaging, and computed tomography (CT). Endoscopy is the gold standard for the assessment of the large bowel and proximal small intestine in patients with IBD allowing the biopsy of the visualized bowel. Positron emission tomography (PET) and PET/CT with Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is a functional imaging method used to detect abnormalities in glucose metabolism in a variety of disorders. FDG accumulates mainly in tumours, but increased uptake and retention has been shown also in lesions with a high concentration of inflammatory cells, such as granulocytes and activated macrophages. Recent literature data demonstrate that FDG-PET and PET/CT may be useful noninvasive tools for identifying and localizing active IBD. In patients with an established diagnosis of IBD, FDG-PET and PET/CT may provide information about disease activity, location and extent of the disease within the intestinal tract, allowing early recognition of disease relapse and possible complications. Furthermore, these techniques may play a role in assessing the treatment response to medical therapy in patients with IBD.

The increasing availability of Ga DOTA somatostatin analogues (SSA), at least in Europe, is challenging traditional diagnostic paths, such as that using I-metaiodobenzylguanidine (MIBG) in phaeochromocytomas (PCC) and paragangliomas (PGL) [1]. Here, using the PCC/PGL as the model, we discuss whether new better performing radiocompounds necessarily determine the disappearance of the older ones. Working for the development of “tailored medicine” for each individual, and being aware that each individual decision has to be taken in the pragmatic world of cost effectiveness, the main assumptions of our thinking are

In most hypertensive patients, changes in left ventricular systolic and diastolic functions may take place before myocardial hypertrophy occurs. Calcium antagonists, particularly the dihydropyridines, can effectively prevent and treat cardiac complications of hypertension. Felodipine, a dihydropyridine calcium antagonist with high vascular selectivity, appears to act on vascular myogenic tone by affecting the voltage-dependent calcium channels. In the present study, the left ventricular function of 15 patients with mild-to-moderate hypertension (mean age, 57.8 years) was monitored using radionuclide angiography. After a 4-week washout period and then after a 4-week treatment period with extended-release felodipine (10 mg/day in a single daily dose), the patients underwent 24-hour ambulatory blood pressure monitoring and radionuclide angiography at rest and after exercise (75 W for women and 100 W for men). Felodipine significantly reduced systolic, diastolic, and mean blood pressures without significantly affecting heart rate. Ventricular function also significantly improved after felodipine treatment, particularly during diastole. In its extended-release formulation, felodipine significantly reduces patients' blood pressure and considerably improves ventricular function both at rest and under stress. Its potential as an efficacious long-term treatment for hypertension and its associated complications is clearly demonstrated.

Positron emission tomography (PET) is an imaging technique that provides direct measurements of receptor binding in neurons. The present study was performed to find reasons for the common observation of rapid metabolism of receptor radioligands during time of a brain PET scan. To this aim, the 1-h phase during which imaging-data are acquired was evaluated by using a pharmacokinetic approach. The values of half-lives, volumes of distribution, and dilution calculated for a set of metabolite corrected plasma curves of D2-receptor radioligand [11C]raclopride (PETc) during 50 min after radioligand injection in tracer dose were compared with the reference values obtained from a set of plasma curves (REFc) during 30 h after i.v. infusion of unlabelled raclopride in pharmacological doses. We found that the half-life of PETc correspond to the distribution half-life of REFc. Accordingly, the distribution volume during the terminal phase of PETc (13.6 ± 10.8 L) was significantly lower than that during the terminal phase (82.2 ± 30.5 L) and at steady state (59.4 ± 20 L) for REFc, and the dilution of raclopride in body for PETc at 50 min was 38 L, whereas it was 1015 L for REFc at 30 h. The [11C]raclopride in plasma at 50 min was higher (10% of dose) than the value for unlabelled raclopride at 30 h (4%). We concluded that the kinetic behavior of the radiolabelled drug [11C]raclopride during the 1 h time of a PET corresponds to the distribution phase. The high percentage of [11C]raclopride in plasma during this phase is a likely reason for the observed rapid radioligand metabolism. J. Cell. Physiol. 227: 1663–1669, 2012. © 2011 Wiley Periodicals, Inc.

Diagnostic imaging in the twentieth century was mainly based on two separate universes: (1) the morpho-structural, where information on anatomy and structures is acquired, having pathology as the gold standard, and (2) the functional, where normal and altered functions are analyzed, with pathophysiology as the reference.

The aims of this study are: (a) to evaluate the reliability of Multidetector Computed Tomography Enteroclysis (MDCT-E) and 99mTc-HMPAO labeled leukocyte scintigraphy (TLLS), in inflammatory bowel disease, (b) to test the accuracy of the two techniques with regard to their histological results, (c) to define how each technique can influence the natural course of inflammatory bowel disease (IBD), (d) to assess the potential value of the two techniques combined. Thirty-seven patients with suspected IBD underwent MDCT-E and TLLS. We made a separate assessment of the results shown by the two methods and then compared and contrasted the histological results of the two. The latter, however, were either disappointing or not available in 15 patients who, for this reason, had to be dismissed from the study. As result, the number of participants eventually dropped to 22 subjects: 12 women, 10 men with an average age of 44 years. MDCT-E and TLLS were successful in all patients. Sensitivity, specificity, and efficiency values have been reported as follows: The two techniques can be employed in different stages of the natural course of the disease. In our experience, TLLS proved itself to be useful in the diagnosis of the disease and the assessment of its development. Conversely, MDCT-E proved itself to be more reliable in identifying the seat and the extent of the disease inside and outside the bowel wall as well as potential intra-peritoneal and extra-intestinal complications. The combined use of the two methods represents the Criterion Standard for diagnosing IBD with imaging.

Radiobiology is the science of the interaction of ionizingradiations with living tissues. To begin with we have beenunaware of the potential hazard resulting from the exposureto ionizing radiations and for decades no health control orphysical measurement of absorbed dose has been put intopractice for exposed medical staff. Following the observa-tion that ionizing radiations may have harmful effects,radiobiology has lived a period of great interest, culminat-ing with the study of atomic bomb survivors and, morerecently, with the Chernobyl accident. Modern radiobiologyfocuses on two major subjects: development of radiobio-logical models for the optimization of therapies using highdoses of ionizing radiations and assessment of risk in thefield of low doses.Radiobiology of high doses of ionizing radiationsIn recent years radionuclide therapy (RNT) has beenincreasingly used and this has prompted us to elaboratemodels to predict toxicity and efficacy of treatment. Atreatment planning approach to RNT more and more willeventually require incorporation of radiobiological consid-erations of therapeutic radiopharmaceuticals [1, 2]. Thedevelopment of radiobiological models for treatmentplanning, however, is still at an early stage of developmentas compared to external beam radiotherapy (EBRT). Todate, most radiobiological models of RNT have been basedon the extrapolation of data obtained following homoge-neous exposures to acute single or fractionated doses ofEBRT and have assumed that EBRT and RNT administereddoses have biological equivalence.Several differences exist, however, between RNT andEBRT: in RNT the radiation dose is delivered to the tumourcells by continuous, but declining, exposure with a lowdose rate (LDR) that is a function of the initial uptake,cellular distribution, residence time, radionuclide half-lifeand energy. The average dose rate for RNT is typically ofthe order of 2–8 Gy/day, and the maximum absorbed dosemay be up to 50 Gy delivered over a period of many days.This is in marked contrast to the situation with EBRT,where the dose is delivered at a constant high dose rate(HDR), typically 1–5 Gy/min [3].Emerging evidence suggests that the mechanisms bywhich cells respond to LDR radiation exposures arefundamentally different from those occurring at HDR withEBRT [1, 4]. The combination of prolonged response,limited toxicity and the ability to treat on multipleoccasions suggests that the mechanism of action of LDR

To determine whether stress–rest myocardial perfusion single-photon emission (MPS) computed tomography improves coronary heart disease (CHD) risk classification in diabetic patients. In 822 consecutive diabetic patients, risk estimates for a CHD event were categorized as 0% to

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Health is priceless, but health care has a budget. In the era when the dream of personalized medicine may become a reality, there are not enough resources to allow the best diagnostic or therapeutic strategy in every situation. An individual is by definition different from all others. Because

In the present diagnostic scenario, because it is difficult to question the primary role of PET/CT, PET/MR imaging has to demonstrate, at least to some extent, when its preference is justified despite its higher cost and more complex management—the topic of an article in this issue of The Journal

Multiple myeloma (MM) is a neoplastic monoclonal proliferation of plasma cells, mainly involving bone marrow. To properly stage and manage patients with MM the clinician needs, at first, a complete skeletal survey, being more rarely present also extra skeletal locations. Today none of the available diagnostic imaging methods is able alone to answer to all the questions regarding staging, treatment, and follow up. Continuing to be alive the role of traditional radiology, implemented information can be added by CT and MRI. Concerning nuclear medicine, bone scintigraphy is affected by its low sensitivity. Tc-99m MIBI has been proposed in staging and in follow up, with most relevant clinical information deriving from the correlation of its whole body uptake's distribution with extent and activity of the disease. The prognostic value of MIBI has also been demonstrated. PET-FDG has been proposed in MM for its ability to detect whole-body metabolic active disease, giving relevant information in staging and prognosis. First studies have demonstrated that PET-FDG is more sensitive than other imaging modalities for localizing extra medullary sites of disease.