Michael K. O'Connor

Bone density and fracture risk in men

We evaluated different definitions of osteoporosis in a population‐based sample of 348 men (age 22–90 years) compared with 351 women (age 21–93 years). Thirty‐six men (10%) and 46 women (13%) had a history of osteoporotic fracture (hip, spine, or distal forearm due to moderate trauma at ≥ age 35). In logistic regression analysis, osteoporotic fracture risk was associated with bone mineral density (BMD) at all sites (neck, trochanter, total hip, lumbar spine, and total wrist) in both genders (p < 0.001) except spinal BMD in men. After adjusting for age, total hip BMD was the strongest predictor of fracture risk in women (odds ratio [OR] per 1 SD decline, 2.4; 95% confidence interval [CI], 1.6–3.7), while wrist BMD was best in men (OR, 1.5; 95% CI, 1.1–2.0). Among men but not women, bone mineral apparent density (BMAD) was a better predictor of fracture than BMD (wrist BMAD OR, 1.7; 95% CI, 1.3–2.3). Hip BMD/BMAD decreased linearly from age 20 years onward in both genders, while spinal BMD/BMAD declined after age 40 in women but not in men. In both genders, total wrist BMD/BMAD decreased after age 50. By World Health Organization criteria, the age‐adjusted prevalence of osteoporosis at the hip, spine, or wrist was 35% among women ≥50 years of age. A similar approach (BMD > 2.5 SD below the young male mean) produced an osteoporosis prevalence rate in men ≥50 years of age of 19%. Thus, bone density predicts fracture risk in men as it does in women, and the prevalence of osteoporosis in men, using sex‐specific normal values, is substantial. These observations indicate a need for better prevention and treatment strategies for men.

EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology

The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.

Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women

We report a 4‐year randomized, double‐blind, placebo‐controlled clinical trial in 236 normal postmenopausal women (mean age ± SE, 66.3 ± 0.2 years) who were randomized to a calcium (1600 mg/day as the citrate) or placebo group. The women were seen every 6 months; 177 completed the trial. Net percentage changes in each group are given relative to baseline. The differences in net percentage changes (calcium group minus placebo group) in medians were: for lumbar spine bone density, 2.0% (p < 0.001) at year 1 and 0.3% (not significant) at year 4; for proximal femur bone density, 1.3% (p = 0.003) at year 1 and 1.3% (p = 0.015) at year 4; and for total body bone mineral, 0.4% (p = 0.002) at year 1 and 0.9% (p = 0.017) at year 4. Similar differences at year 4 were: −18.9% (p = 0.002) for parathyroid hormone (PTH), −11.9% (p = 0.026) for serum osteocalcin, and −32.2% (p = 0.003) for urine free pyridinoline. We conclude that long‐term administration of calcium supplements to elderly women partially reverses age‐related increases in serum PTH level and bone resorption and decreases bone loss. However, the effects on bone loss were weaker than those reported for estrogen, bisphosphonates, or calcitonin therapy, indicating that calcium supplements alone cannot substitute for these in treating established osteoporosis. Nonetheless, because of their safety, high tolerance, and low expense, calcium supplements may be a useful preventive measure for elderly postmenopausal women whose bone mineral density values are normal for their age.

Subtraction ictal SPET co-registered to mri in partial epilepsy : Description and technical validation of the method with phantom and patient studies

Computer-aided subtraction of the co-registered and normalized interictal from the ictal single photon emission tomography (SPET) scan, followed by co-registration to the magnetic resonance image, may improve the utility of ictal SPET in the localization of partial epilepsy. This paper describes and technically validates our method. The SPET to SPET co-registration was tested using six sequential 99Tcm brain phantom SPET images of different known positions (15 matches). The registration error was determined by multiplying the calculated match transformation matrix by the inverse of the known transformation matrix. The ‘worst case’ co-registration error was less that one voxel diameter in all cases (median 3.2 mm, range 1.2–4.8 mm). For interictal to ictal SPET registrations in 10 consecutive intractable partial epilepsy patients, a similar root mean square distance (RMSD) between corresponding points on the matched scans was found as for the phantom studies (median 2.2 vs 2.6 mm). The appropriateness of our normalization was studied by comparing the pixel intensity distributions between the matched scans, and by analysing the subtraction pixel intensity distribution. The pixel intensity distribution for both the normalized phantom, and paired normalized patient studies, were closely matched to each other except for the extreme values, which in clinical situations likely represent regions of ictal activation or depression. The subtraction image intensity distributions were symmetrically centred on zero for all values up to at least within the 5th to 95th centile range, confirming good normalization for the ‘non-activated’ pixels. Also, a linear relationship was demonstrated between the measured pixel intensity on the phantom scans and the true changes in 99Tcm activity based on its decay constant. The results of this study demonstrate that our method produces accurate SPET to SPET co-registration, and appropriate SPET normalization, thereby allowing a valid ictal subtraction image to be derived.

In vivo sodium iodide symporter gene therapy of prostate cancer

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of thyroid-specific expression of the sodium iodide symporter (NIS). Here we explore the efficacy of a novel form of gene therapy using adenovirus-mediated in vivo NIS gene transfer followed by 131I administration for treatment of prostate cancer. Prostate cancer xenografts in nude mice injected with an adenovirus carrying the NIS gene linked to the cytomegalovirus (CMV) promoter revealed highly active uptake of radioiodine. Following administration of 3 mCi of 131I, we observed an average tumor volume reduction of 84 ± 12%. These results show for the first time that in vivo NIS gene delivery into non-thyroidal tumors is capable of inducing accumulation of therapeutically effective radioiodine doses and might therefore represent an effective and potentially curative therapy for prostate cancer.

Development of a test to measure gastric accommodation in humans

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of (99m)Tc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 +/- 11 (SE) ml and mean postprandial volume was 690 +/- 32 ml (P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia

In vitro validation of a simple tomographic technique for estimation of percentage myocardium at risk using methoxyisobutyl isonitrile technetium 99m (sestamibi)

With the advent of technetium 99m-labeled myocardial blood flow agents, there is a need for a simple technique for quantitation of infarcted or jeopardized myocardium (IM). This study provides an in vitro validation of a simple technique based upon the analysis of three short-axis slices through the heart following emission computed tomography. All acquisitions were performed using a static cardiac phantom containing pertechnetate Tc 99 m. Activity in the phantom was adjusted so that the count density and myocardial-to-background ratio were comparable to those observed in patients. Plastic insets (range of sizes = 4%–72% of myocardium) were used to simulate transmural infarctions. Eighteen studies were acquired, each over 180° into a 64 × 64 matrix. Data were reconstructed using a Ramp Hanning filter with cut off at 0.7 times the Nyquist frequency. Short-axis slices of the myocardium were then generated, and representative apical (A), mid-ventricular (MV), and basal (B) slices were selected. For each slice, a circumferential profile was generated, and the average radius (R) was measured. The fraction (F) of the profile falling below a threshold value was considered to represent IM. Total IM was given by %IM =100 x (RBFB +RMVFMV + 0.67RAFA)/(RB +RMV + 0.67RA), where the subscripts to R and F refer to the relevant short-axis slices. For a threshold set at 60% of peak, measured IM agreed closely with true IM (R2=0.98, measured IM =1.01 x true IM −1.35). Measurement of % IM was not distorted by variations in slice radius or in slice selection. Maximum error in % IM occurred with a change in location of the infarct (approximately 4% for opposing walls). This technique permits rapid and accurate assessment of % IM with99mTc-labeled myocardial blood flow agents.

Dedicated Dual-Head Gamma Imaging for Breast Cancer Screening in Women with Mammographically Dense Breasts

PURPOSE To compare performance characteristics of dedicated dual-head gamma imaging and mammography in screening women with mammographically dense breasts. MATERIALS AND METHODS Asymptomatic women (n = 1007) who had heterogeneously or extremely dense breasts on prior mammograms and additional risk factors provided informed consent to enroll in an institutional review board-approved HIPAA-compliant protocol. Participants underwent mammography and gamma imaging after a 740-mBq (20-mCi) technetium 99m sestamibi injection. Reference standard (more severe cancer diagnosis or 12-month follow-up findings) was available for 936 of 969 eligible participants. Diagnostic yield, sensitivity, specificity, and positive predictive values (PPVs) were determined for mammography, gamma imaging, and both combined. RESULTS Of 936 participants, 11 had cancer (one with mammography only, seven with gamma imaging only, two with both combined, and one with neither). Diagnostic yield was 3.2 per 1000 (95% confidence interval [CI]: 1.1, 9.3) for mammography, 9.6 per 1000 (95% CI: 5.1, 18.2) for gamma imaging, and 10.7 per 1000 (95% CI: 5.8, 19.6) for both (P = .016 vs mammography alone). One participant had a second ipsilateral cancer detected with gamma imaging only. Prevalent screening gamma imaging demonstrated equivalent specificity relative to incident screening mammography (93% [861 of 925] vs 91% [840 of 925], P = .069). Of eight cancers detected with gamma imaging only, six (75%) were invasive (median size, 1.1 cm; range, 0.4-5.1 cm); all were node negative. The ratio of the number of patients with breast cancer per number of screening examinations with abnormal findings was 3% (three of 88) for mammography and 12% (nine of 73) for gamma imaging (P = .01). The number of breast cancers diagnosed per number of biopsies performed was 18% (three of 17) for mammography and 28% (10 of 36) for gamma imaging (P = .36). CONCLUSION Addition of gamma imaging to mammography significantly increased detection of node-negative breast cancer in dense breasts by 7.5 per 1000 women screened (95% CI: 3.6, 15.4). To be clinically important, gamma imaging will need to show equivalent performance at decreased radiation doses.

Determinants of Bone Loss from the Femoral Neck in Women of Different Ages

An age‐stratified sample of 304 women from Rochester, Minnesota, aged 30–94 years (median 60 years) at baseline underwent measurement of femoral neck bone mineral density (BMD) over a follow‐up period extending to 16 years. The average rate of change in femoral neck BMD was −1.0% per year (range −10.0% to +13.4%) and did not vary significantly with age. Because there was no marked increase in the rate of loss around the time of menopause, nor convincing evidence of there being a subset of fast losers, there was fairly good tracking of individual values over time; the correlation of baseline with femoral neck BMD values 16 years later was 0.83. Although a large number of potential determinants was assessed, the only consistent predictor of femoral neck bone loss in women of different ages was baseline femoral neck BMD (r = −0.15; p = 0.023). Otherwise, different sets of risk factors were identified for premenopausal women, women within 20 years of menopause, and women 20 years or more postmenopausal, but the predictive power of these different multivariate models was modest. Nonetheless, these data indicate that femoral neck BMD is quite predictable for extended periods of time. This is reassuring with respect to the use of statistical models that incorporate such data to estimate future fracture risk.