The Role of Myocardial Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events at 1 Year Follow-Up: A Single Center's Experience.

BACKGROUND: Myocardial perfusion imaging via single-photon emission computed tomography (SPECT MPI) is a well-established method of diagnosing coronary artery disease (CAD). The purpose of this study was to assess the role of SPECT MPI in predicting major cardiovascular events. METHODS: The study population was composed of 614 consecutive patients (mean age: 67 years, 55% male) referred for SPECT MPI due to symptoms of stable CAD. The SPECT MPI was performed using a single-day protocol. We conducted a follow-up on all patients at 12 months via a telephone interview. RESULTS: The majority of our patients (78%) presented findings suggestive of reversible ischemia, fixed defects or both. Extensive perfusion defects were found in 18% of the population, while LV dilation was found in 7%. During the 12-month follow-up, 16 deaths, 8 non-fatal MIs and 20 non-fatal strokes were recorded. There was no significant association of SPECT findings with the combined endpoint of all-cause death, non-fatal MI and non-fatal stroke. The presence of extensive perfusion defects was an independent predictor of mortality at 12 months (HR: 2.90, 95% CI: 1.05, 8.06, p = 0.041). CONCLUSIONS: In a high-risk patient population with suspected stable CAD, only large reversible perfusion defects in SPECT MPI were independently associated with mortality at 1 year. Further trials are needed to validate our findings and refine the role of SPECT MPI findings in the diagnosis and prognosis of cardiovascular patients.

Radiotherapy for breast cancer induced long-term diminished accumulation of radiotracer on bone scan of the irradiated ribs.

Radiotherapy may result in long term effects and composition alterations in bones. Bone scintigraphy after radiotherapy may demonstrate decreased skeletal uptake; however, this is a transient effect with bone scan normalized after a few years. We describe a case of a 31-year-old female patient treated for left breast cancer with chemotherapy and radiotherapy, exhibiting reduced and diffuse diphosphonate uptake in the heavily irradiated sections of left ribs, even twelve years post-treatment. Similarly, quantitative computed tomography indicated altered bone composition. To our knowledge this is the first case describing such a long radiation side effect in breast cancer treatment.

Alterations of p53 and Rb Pathways Are Associated with High Proliferation in Bladder Urothelial Carcinomas.

BACKGROUND/AIM: Since most cancers are associated with alterations of the p53 and Rb pathways, the expression of p53, p21, Rb, p16, p27, cyclin D1, cyclin A, cyclin B1 and Ki67 proteins were analyzed in bladder urothelial carcinomas (BUC). MATERIALS AND METHODS: One hundred twenty-two cases of BUC were studied by immunohistochemistry. RESULTS: The pathways p53/p21 and Rb/p16/cyclin D1 exhibited alterations in 81/115 and 63/84 cases, respectively. Alterations of the p53/p21 and Rb/p16/cyclin D1 pathways were positively correlated with high cyclin A expression. High expression of p53, Ki67, cyclin A and cyclin B1 was inversely correlated with the papillary morphology of the tumor and positively with tumor grade and T-stage. CONCLUSION: The results showed that a) alterations of the p53 and Rb pathways are associated with high proliferation of tumor cells in BUC and b) high expression of cell-cycle proteins is associated with adverse histopathological parameters of these tumors.

99mTc-Tetrofosmin Uptake Correlates with the Sensitivity of Glioblastoma Cell Lines to Temozolomide.

99mTc-tetrofosmin (99mTc-TF) is a single-photon emission computed tomography tracer that has been used for brain tumor imaging. The aim of the study was to assess if 99mTc-TF uptake by glioblastoma cells correlates with their response to temozolomide (TMZ). We investigated the correlation of TMZ antitumor effect with the 99mTc-TF uptake in two glioblastoma cell lines. The U251MG cell line is sensitive to TMZ, whereas T98G is resistant. Viability and proliferation of the cells were examined by trypan blue exclusion assay and xCELLigence system. Cell cycle was analyzed with flow cytometry. The radioactivity in the cellular lysate was measured with a gamma scintillation counter. TMZ induced G2/M cell cycle arrest in U251MG cells, whereas there was no effect on cell cycle in T98G cells. Lower 99mTc-TF uptake was observed in U251MG cells that were exposed to TMZ compared to control (P = 0.0159). No significant difference in respect to 99mTc-TF uptake was found in T98G cells when exposed to TMZ compared to control (P = 0.8). With 99mTc-TF, it was possible to distinguish between TMZ-sensitive and resistant glioblastoma cells within 6 h of treatment initiation. Thus, 99mTc-TF uptake may consist a novel approach to assess an early response of glioblastoma to chemotherapy and deserves further investigation.

Direct total body 214Bi measurements and their implications for radon dose assessment.

Direct 214Bi bioassays may elucidate some of the uncertainties related to the relationship between the ambient concentration of radon and its short-lived decay products and the corresponding radiation burdens of individual human subjects. Sequential total body 214Bi activity measurements were carried out on a group of 67 healthy adult volunteers living in a region with moderate airborne radioactivity and conducting similar daily activities using a whole-body counter equipped with sixteen NaI(Tl) detectors. The total body 214Bi activity in the studied subjects was related to gender, fat-free mass and the season of the year. Approximately 95% and 92% of the 214Bi activity measured during the cold seasons of the year in men and women, respectively, was attributed to radon progeny inhalation. Following acute exposure to high airborne radioactivity over a short time period, the 214Bi enhancement in a volunteer decreased exponentially with time post-exposure, with a half-time of about 40 min. Taking into account the anticipated low 214Bi activity in the vast majority of individuals, and the uncertainties in 214Bi biodistribution even during counting, accurate measurements can be obtained using high-sensitivity whole-body counters with almost geometrical invariant counting efficiency.

Technical Note: Independent component analysis for quality assurance in functional MRI.

PURPOSE: Independent component analysis (ICA) is an established method of analyzing human functional MRI (fMRI) data. Here, an ICA-based fMRI quality control (QC) tool was developed and used. METHODS: ICA-based fMRI QC tool to be used with a commercial phantom was developed. In an attempt to assess the performance of the tool relative to preexisting alternative tools, it was used seven weeks before and eight weeks after repair of a faulty gradient amplifier of a non-state-of-the-art MRI unit. More specifically, its performance was compared with the AAPM 100 acceptance testing and quality assurance protocol and two fMRI QC protocols, proposed by Freidman et al. ["Report on a multicenter fMRI quality assurance protocol," J. Magn. Reson. Imaging 23, 827-839 (2006)] and Stocker et al. ["Automated quality assurance routines for fMRI data applied to a multicenter study," Hum. Brain Mapp. 25, 237-246 (2005)], respectively. RESULTS: The easily developed and applied ICA-based QC protocol provided fMRI QC indices and maps equally sensitive to fMRI instabilities with the indices and maps of other established protocols. The ICA fMRI QC indices were highly correlated with indices of other fMRI QC protocols and in some cases theoretically related to them. Three or four independent components with slow varying time series are detected under normal conditions. CONCLUSIONS: ICA applied on phantom measurements is an easy and efficient tool for fMRI QC. Additionally, it can protect against misinterpretations of artifact components as human brain activations. Evaluating fMRI QC indices in the central region of a phantom is not always the optimal choice.

The effect of menarche age, parity and lactation on bone mineral density in premenopausal ambulatory multiple sclerosis patients.

Although pregnancy and breast-feeding do not have any deleterious effect on disease activity in female multiple sclerosis (MS) patients, their role on bone mineral density (BMD) and osteoporosis risk is unknown. We investigated the role of age at menarche, parity and lactation on BMD expressed as percentage of the mean BMD (%BMD) in 46 pre-menopausal ambulatory female MS patients using dual-energy X-ray absorptiometry (DXA) scans in lumbar spine (LS) and hip. MS female patients with age at menarche ≥13 years old had reduced %BMD compared to those with menarche age <13 years (95.2±10.7 vs 102.1±13.3, p=0.05 in LS; 90.5±12.6 vs 99.8±12.6, p=0.02 in hip). Parity did not result in any statistically significant changes in either LS or hip. Patients that breastfed their offspring compared to those that did not had significantly lower BMD in both LS (93.9±9.3 vs 110.7±15.6, p=0.004) and hip (91.6±10.7 vs 105.6±15.3, p=0.02). MS female patients with menarche at age≥13 years and those who breastfed their offspring may have reduced BMD. Larger studies are needed to verify these findings and establish a definite role of menarche age and breast feeding with BMD.

Gender specific association of decreased bone mineral density in patients with epilepsy.

OBJECTIVE: To evaluate whether epilepsy or certain antiepileptic drugs render patients prone to develop low bone mineral density (BMD) and osteoporosis risk. METHODS: Thirty-eight (27 males, 11 females) consecutive adult epileptic patients receiving antiepileptic drugs (AEDs) and 71 control individuals matched for race, gender, age and body mass index (BMI) were subjected to dual energy X-ray absorptiometry (DXA). RESULTS: The mean lumbar spine and total hip BMD values were lower in the patients compared to control group (0.90±0.24 g/cm2 vs 1.04±0.14 g/cm2, p<0.001 and 0.92±0.14 g/cm2 vs 0.99±0.13 g/cm2, p=0.02, respectively). At the same skeletal sites, male patients had significantly reduced BMD compared to control males (0.90±0.21 g/cm2 vs 1.03±0.15 g/cm2, p=0.004 and 0.93±0.14 g/cm2 vs 1.02±0.13 g/cm2, p=0.009, respectively) while there was a trend but no significant differences in females. This BMD reduction was independent of AED type. CONCLUSION: Adult epileptic, predominantly male patients have lower BMD and could be screened with densitometry for early diagnosis and prevention of osteoporosis.

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT).

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25-75 micron-wide microplanar beams separated by wider (100-400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.

Relationships between body composition analysis measures in Greek women and US white women.

We investigated the regional changes in body composition relative to age, in healthy Caucasian women living in the Mediterranean area. Body composition of total and subtotal body was measured, and fat mass (FM) ratios along with FM and lean mass (LM) indices were calculated in 330 women aged 20-85 years, using DXA. Data were compared with the NHANES reference database. Peak bone mineral density and bone mineral content of total body were 1.149 g/cm(2) and 2,209 g and were achieved between ages 41 and 50. Peak %FM of total body, FM index (FMI; FM/height(2)), FM of trunk to legs, and FM of trunk to limbs were 41.5%, 13.69 kg/m(2), 1.623, and 1.14, respectively. Peak %FM and FMI were achieved between 61 and 70 years. Unlike US counterparts, in our series, both FM ratios showed a propensity for women to accrue fat in the trunk following the android pattern of fat distribution. Peak LM index for total body (LMI; LM/height(2)) and limbs (ASMMI; appendicular skeletal muscle mass/height(2)) was 18.08 kg/m(2) and 7.33 kg/m(2), respectively, and was achieved between 61 and 70 years. For Greeks, the ASMMI was greater from 55 years onwards. Greek women have increasing bone mass in early adulthood followed by significant decline during fifties and onwards. Compared with US white women, Greek women have significantly greater truncal fat for all ages, implying a greater risk of obesity-associated diseases. Middle-aged and older Greek women have greater appendicular skeletal muscle mass, which may eliminate the overall risk of sarcopenic obesity.

Comparison of (99m)tc-tetrofosmin and (99m)tc-sestamibi uptake in glioma cell lines: the role of p-glycoprotein expression.

(99m)Tc-Tetrofosmin ((99m)Tc-TF) and (99m)Tc-Sestamibi ((99m)Tc-MIBI) are SPECT tracers that have been used for brain tumor imaging. Tumor's multidrug resistance phenotype, namely, P-glycoprotein (p-gp), and the multidrug resistance related proteins (MRPs) expression have been suggested to influence both tracers' uptake. In the present study we set out to compare (99m)Tc-TF and (99m)Tc-MIBI uptake in high-grade glioma cell lines and to investigate the influence of gliomas p-gp expression on both tracers' uptake. We used four glioma cell lines (U251MG, A172, U87MG, and T98G). The expression of p-gp protein was evaluated by flow cytometry. Twenty µCi (7.4·10(5) Bq) of (99m)Tc-TF and (99m)Tc-MIBI were used. The radioactivity in the cellular lysate was measured with a dose calibrator. P-gp was significantly expressed only in the U251MG cell line (P < 0.001). In all gliomas cell lines (U251MG, U87MG, A172, and T98G) the (99m)Tc-TF uptake was significantly higher than (99m)Tc-sestamibi. The U251MG cell line, in which significant p-gp expression was documented, exhibited the strongest uptake difference. (99m)Tc-TF uptake was higher than (99m)Tc-MIBI in all studied high-grade glioma cell lines. Thus, (99m)Tc-TF may be superior to (99m)Tc-MIBI for glioma imaging in vivo.

Measurement uncertainties in whole body counting and radon progeny.

Measurement uncertainty is an important quality index in gamma spectrometry related to the level of bias and precision involved in the measuring procedure. Quality control measurements during the commissioning of a 16-input whole body counter showed substantial deviations between the experimentally determined precision and the theoretical estimation, indicating either equipment malfunction or lack of reproducibility of the experimental setup. In this study, the role of the magnitude and variability of airborne background radiation present in the counting room and the human body in the deterioration of the precision of counters employing NaI(Tl) detectors was investigated. Correction methods and actions based on case-specific background features were developed and applied. The experimental observations were benchmarked using a mathematical model of the counter. The efficacy of the developed methods was tested by measurements, and updated precision values were obtained. Quasi-equilibrium between the gamma-emitters Bi and Pb in the counting room and the human body is a prerequisite for accurate direct low-level radioactivity measurements in the human body.

Renal cell carcinoma: value of multiphase MDCT with multiplanar reformations in the detection of pseudocapsule.

OBJECTIVE: The purpose of this study was to assess the diagnostic performance of four-phase (unenhanced, arterial, portal, and nephrographic-excretory) MDCT with multiplanar reformations in the detection of pseudocapsule of renal cell carcinoma (RCC). MATERIALS AND METHODS: In a retrospective study of 29 histologically proven RCCs in 29 patients (17 men, 12 women; mean age, 59 years), examinations were performed with a 16-MDCT scanner. The protocol included unenhanced and three-phase (arterial, portal, and nephrographic-excretory) contrast-enhanced CT. The data were analyzed by two reviewers blinded to the histopathologic results. Any discrepancy was resolved by consensus. The presence of a regular, high- or low-attenuation halo surrounding a renal neoplasm was considered to represent renal pseudocapsule. The accuracy of MDCT in the detection of pseudocapsule with the histopathologic results as the standard of reference was evaluated. Unenhanced transverse images and multiplanar reformations in the transverse, coronal, and sagittal planes of each contrast-enhanced phase were separately analyzed. The chi-square two-way test was used to compare each CT phase and multiplanar reformation with histologic results. RESULTS: The mean diameter of RCCs on CT scans was 5.6 cm (range, 2.8-15 cm), in accordance with the pathologic result. MDCT enabled detection of renal pseudocapsule in 20 of 29 RCCs with 83% sensitivity, 80% specificity, 95% positive predictive value, 50% negative predictive value, and 83% overall accuracy. Imaging in the portal and nephrographic phases with coronal and sagittal reformations proved more accurate in the detection of pseudocapsule (p < 0.05). CONCLUSION: Multiphase MDCT with multiplanar reformations had satisfactory results in the detection of renal pseudocapsule in RCC.

Health physics aspects in treatment rooms after 18-MV X-ray irradiations.

Delayed activation products contribute to the exposure of the staff operating high-energy accelerators. Induced activity was studied in a treatment room following 18-MV X-ray irradiations using a hand-held system that allows both dose rate measurements and spectroscopic analysis. The major activation products and the corresponding nuclear reactions were identified. At the majority of the studied locations, ß(+) emitters were the main short-term dose contributors. The time variation of the absorbed dose rate in a treatment room during the first 20-min post-irradiation was represented by the sum of two exponential components with half-lives of 1-2 min and either 4 or 10 min, depending on the location in the room. Components with a half-life of hours or days contribute <1 % to the initial dose rate. The activation of some accessories, such as iron filters and portal imagers, deserve special attention. The collection of such data with the proposed method allows the development of optimised working protocols at each treatment room.

Body composition in ambulatory patients with multiple sclerosis.

The aim of this study was to compare between ambulatory patients with multiple sclerosis (MS) and control subjects, bone mineral density (BMD), and body composition, that is, percent of bone minerals (M%), fat (F%), and remaining substances (L%). Total body composition and BMD were measured by dual-energy X-ray absorptiometry in 68 patients with definite MS and Expanded Disability Status Scale (EDSS) score ≤ 6.5 (41 females and 27 males) and 114 control individuals (72 females and 42 males). The amount of F%, L%, M%, and BMD in the whole body, arms, and trunk was not statistically different between MS patients (males and females) and controls, except in the lower extremities of female patients where there was increased F% and reduced L% compared with controls. There were no correlations between F%, L%, M%, and BMD at any anatomic region with EDSS or the cumulative corticosteroid dose. The reduced L% in the lower extremities of female patients suggests a possible increased subsequent risk of osteoporosis in the legs. Brief steroid courses administered during disease exacerbations in ambulatory MS patients did not result in obvious adverse consequences.

Bone mineral density in ambulatory patients with multiple sclerosis.

Multiple sclerosis (MS) may be associated with reduced bone mass and higher frequency of osteoporosis. Femoral and spinal bone mineral density (BMD) in 70 ambulatory MS patients (46 females and 24 males) was compared with 100 sex-, age-, and BMI-matched control individuals. BMD was reduced in male patients (lumbar spine 0.976 ± 0.114 g/cm(2) compared with 1.059 ± 0.147 g/cm(2) in controls, p = 0.024, total hip 0.946 ± 0.136 g/cm(2) compared to 1.036 ± 0.118 g/cm(2) in controls, p = 0.008, femoral neck 0.812 ± 0.136 g/cm(2) compared with 0.887 ± 0.135 g/cm(2) in controls p = 0.042), and only in the total hip in female patients (0.88 ± 0.127 g/cm(2) compared with 0.935 ± 0.112 g/cm(2) in controls, p = 0.018). Multivariate analysis demonstrated that the predominantly affected site was the hip. MS patients exhibit increased frequency of low bone mass compared with controls. Further studies should assess the etiologic factors and employ appropriate therapies.

Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma.

The purpose of this study is to test the hypothesis that gold nanoparticle (AuNP, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNP-mediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective at 42 Gy than at 30 Gy (both at 68 keV median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose ( approximately 42 Gy), 68 keV was more effective than 157 keV. Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 50%) and increasing long-term survivals. It is concluded that gold nanoparticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.

Photon activation therapy and brachytherapy.

PURPOSE: In photon activation therapy (PAT), energy deposition at critical sites within a tumor can be increased by complexing the DNA with higher Z atoms, and provoking the emission of Auger electrons after inducing a photoelectric effect. This in vivo study evaluates the hypothesis using X-rays from palladium-103 seeds to excite the L-edge of platinum (Pt) atoms bound to the DNA of cancerous cells. METHODS AND MATERIALS: Pt (II) tetrakis(N-methyl-4-pyridyl) porphyrin chloride was used to locate Pt atoms adjacent to the DNA of the KHJJ murine mammary carcinoma; a 2.3-mCi palladium-103 seed was implanted in the tumor. RESULTS: The tumor periphery received subtherapeutic doses. The rate of tumor growth in mice treated with PAT was slower than in mice treated with brachytherapy only. CONCLUSIONS: The tumor growth delay for PAT-treated mice is attributed to Auger emission from Pt atoms that produced substantial local damage. However, other co-existing mechanisms cannot be ruled out.

Radiation burden of patients undergoing endovascular abdominal aortic aneurysm repair.

INTRODUCTION: Endovascular repair of abdominal aortic aneurysm (EVAR) requires the patient's extended exposure to x-rays, before, during, and after the intervention. The aim of this study was to determine the radiation exposure of patients undergoing EVAR and to assess the probability for the induction of both late and early radiation-related effects. METHODS: During the period of May 2006 to December 2007 EVAR was carried out in 62 patients using a mobile C-arm unit. The following dosimetric quantities were assessed: fluoroscopy time, cumulative dose in air, dose-area product, field area, and peak skin dose. RESULTS: The duration of fluoroscopy and the body mass index were found to be the main factors that influence the radiation burden in our hospital. The mean effective dose per procedure, 6.2 mSv, was between that from a planar coronary angiography and a coronary angioplasty. Taking into account the computed tomography (CT) procedure-related angiographies carried out during the first year, patients receive a total effective dose of about 62 mSv within the first year. In vivo dosimetry showed that the peak skin dose was linearly correlated with cumulative dose in air and did not exceed 1.0 Gy, ie, it was less than the threshold for any acute skin reaction. CONCLUSION: Repair of abdominal aortic aneurysm results in substantial radiation burden. Radiation-related risks for carcinogenesis and skin injuries are factors that have to be taken into account in the selection of the strategy of each facility.