Role of myocardial perfusion imaging in risk stratification

This review paper is based on a topic invited for review presented by the first author at the Annual Meeting of Society of Nuclear Medicine of Serbia and Montenegro, September 2003.The optimal management of patients affected by coronary artery disease requires safe and cost-effective techniques for assessing the risk of subsequent cardiac events or the need for surgery. The ideal test should distinguish between high risk patients who will benefit from aggressive management and low risk patients who can be managed conservatively. Stress testing alone is believed to be inadequate for the assessment of risk. Nuclear Medicine techniques have routinely been used in the identification of patients with ischaemic heart disease and those with viable myocardium post myocardial infarction. While the essential methodology for the techniques remains same, the reporting and interpretation criteria for determining future risk are different. For instance, a fixed perfusion defect on stress myocardial perfusion imaging in a patient presenting cardiactype chest pain to the cardiologists for the first time, has a different value from a similar patient being presented to the noncardiologist for major vascular surgery.A review of the literature concerning the current usage of nuclear cardiology techniques in risk stratification is presented

Incidental detection of Os acromiale mimicking a fracture on 18F-Fluoride PET-CT

Os acromiale represents an unfused accessory centre of ossification of the acromion of scapula. It may cause shoulder impingement, rotator cuff tear or degenerative acromio-clavicular joint disease. A 38-year-old male with history of degenerative disc disease presented with persistent backache. MRI of the lumbar spine had earlier showed left paracentral disc protrusion of L5/S1 vertebrae impinging the left S1 nerve root for which the patient underwent fluoroscopic guided nerve root block. Due to persistent bilateral sciatica and worsening leg pain a decompression surgery was planned. A bone scan was requested to exclude other causes of pain prior to surgery for which the patient underwent 18F- Fluoride PET-CT examination. We report a case of incidental detection of Os acromiale mimicking fracture. As the management strategy for both is quite different this case highlights the importance of correct recognition of this identity for appropriate management

The who, when, why, and how of PET Amyloid imaging in management of Alzheimer’s disease-review of literature and interesting images

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided

PET-CT in esophageal cancer management: a cost effectiveness analysis study

The present investigation dealt with the assessment of clinicians perceived views on the impact of PET-CT in esophageal cancer management from practicality, clinical efficacy and cost –effectiveness point of views. Reviews on publication and retrospective data to develop and carry out a decision-making model-based economic evaluation to investigate the relative cost-effectiveness of PET/CT in esophageal cancer management staging compared with conventional pathway. Clinicians identified from patient medical records were included in the survey. Retrospective analysis of patient data from 2001-2008 was taken from esophageal cancer patient medical records and North West Cancer Intelligence Services (NWCIS) database. A decision tree was developed using TREEAGE software. The results of the cost-effectiveness analysis were presented in terms of the incremental cost-effectiveness ratios (I-CERs). PET compared with conventional work-up results for ICER for the strategy estimated at £28,460 per QALY; PET/CT compared with PET for ICER was £ 32,590 per QALY; and the ICER for PET/CT combined with conventional work-up versus PET/CT was £ 44,118. The package became more expensive with each additional diagnostic test added to PET and more effective in terms of QALYs gained. The conventional work-up was the preferred options as probabilistic sensitivity analysis showed at a willingness-to-pay threshold of £ 20,000 per QALY. Result of the current analysis suggested that the use of PET/CT in the diagnosis of esophageal cancer was unlikely to be cost-effective given the current willingness-to-pay thresholds that were accepted in the United Kingdom by decision-making bodies such as the National Institute for Health and Clinical Excellence

The role of PET/CT amyloid Imaging compared with Tc99m-HMPAO SPECT imaging for diagnosing Alzheimer's disease

Background: Imaging such as Tc99m-HMPAO single photon emission computed tomography (SPECT), and positron emission tomography/ computed tomography (PET/CT) amyloid scans are used to aid the diagnosis of Alzheimer’s disease (AD). Objective: We aimed to correlate the ability of these modalities to differentiate Probable AD and Possible AD using the clinical diagnosis as a gold standard. We also investigated the correlation of severity of amyloid deposit in the brain with the diagnosis of AD. Methods: A retrospective study of 47 subjects (17 Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO SPECT and loss of grey-white matter contrast in cortical regions on PET/CT Amyloid scans indicating the presence of amyloid β deposit were qualitatively interpreted as positive for AD. SPECT and PET/CT were also read in combination (Combo reading). The severity of amyloid β deposit was semiquantitatively assessed in a visual binary method using a scale of Grade 0-4. The severity of amyloid β deposit was assessed in a visual binary method and a semi-quantitative method using a scale of Grade 0-4. Results: There was significant correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3% (SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0% (Combo reading) respectively. The grade of amyloid deposition was not significantly correlated with AD (Spearman’s correlation, p=0.687). Conclusion: There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with atypical presentation and indeterminate findings on conventional imaging of Alzheimer’s disease

Cathepsin Z as a novel potential biomarker for osteoporosis

Osteoporosis, one of the most prevalent chronic ageing-related bone diseases, often goes undetected until the first fragility fracture occurs, causing patient suffering and cost to health/social care services. Osteoporosis arises from imbalanced activity of osteoclasts and osteoblasts. Since these cell lineages produce the protease, cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. Cathepsin Z mRNA in human peripheral blood mononuclear cells was significantly differentially-expressed among non-osteoporotic controls, osteopenia and osteoporosis patients (p < 0.0001) and in female osteoporosis patients over the age of 50 years (P = 0.0016). Cathepsin Z mRNA level strongly correlated with low bone mineral density (BMD) (g/cm2), lumbar spine L2-L4 and femoral neck (T-scores) (P = 0.0149, 0.0002 and 0.0139, respectively). Importantly, cathepsin Z mRNA was significantly associated with fragility fracture in osteoporosis patients (P = 0.0018). The levels of cathepsin Z mRNA were not significantly higher in patients with chronic inflammatory disorders in these two groups compared to those without (P = 0.774 and 0.666, respectively). ROC analysis showed that cathepsin Z mRNA has strong diagnostic value for osteoporosis and osteoporotic fracture. The results show for the first time that cathepsin Z could be a future diagnostic biomarker for osteoporosis including female osteoporosis patients over the age of 50 years

Altered levels of mRNAs for calcium binding / associated proteins, Annexin A1, S100A4 and TMEM64 in peripheral blood mononuclear cells are associated with osteoporosis

Background. Osteoporosis is the most common metabolic bone disease in the world. Since osteoporosis is clinically symptomless until the first fracture occurs, early diagnosis is critical. Calcium, along with calcium-binding and calcium-associated proteins, plays an important role in homeostasis, maintaining healthy bone metabolism. This study is aimed at investigating the level of calcium-binding/associated proteins, annexin A1, S100A4, and TMEM64, in peripheral blood mononuclear cells associated with osteoporosis and its clinical significance. Methods. The levels of mRNAs of annexin A1, S100A4, and TMEM64 in human peripheral blood mononuclear cells were evaluated among 48 osteopenia and 23 osteoporosis patients compared to 17 nonosteoporotic controls. Total RNAs were isolated from clinical samples, and quantitation of mRNA levels was performed using real-time quantitative PCR. Results. The levels of mRNAs for calcium-binding proteins, annexin A1 and S100A4, and calcium-associated protein, TMEM64, in human peripheral blood mononuclear cells were significantly reduced in osteopenia and osteoporosis patients compared with nonosteoporotic controls (one-way ANOVA, P < 0.0001, P = 0.039 and P = 0.0195 respectively). Annexin A1 and TMEM64 mRNAs were also significantly reduced in female osteoporosis patients over the age of 50 years compared to nonosteoporotic controls (one-way ANOVA, P = 0.004 and P = 0.0037, respectively). ROC analysis showed that the reduction in the level of mRNA for annexin A1, S100A4, or TMEM64 in the patients’ peripheral blood mononuclear cells has a good diagnostic value for osteoporosis. Conclusions. The results show for the first time that calcium-binding/associated proteins, annexin A1 and TMEM64, could be future diagnostic biomarkers for osteoporosis

Reliability of standardized uptake value normalized to lean body mass using the liver as a reference organ, in contrast-enhanced 18F-FDG PET/CT imaging

Purpose: To evaluate the reliability of standardized uptake value (SUV) normalized to lean body mass for maximum (SULmax) and mean values (SULmean) as well as maximum SUV values (SUVmax) in contrast-enhanced 18F-FDG PET/CT by assessment of inter-reader agreement, using the liver as a reference organ. Materials and methods: 272 images of baseline PET/CT scans were analyzed. A volume of interest (VOI) of 30-mm in diameter was placed by two independent readers in the right liver lobe to measure the parameters. An analysis was performed for the variance, intra-class correlation coefficient (ICC), and Bland-Altman plots. Results and discussion: For Reader 1, the SUVmax ranging from 1.33 to 5.94 (3.20 ± 0.69), SULmean ranging from 0.84 to 3.46 (1.90 ± 0.40) and SULmax ranging from 1.18 to 4.07 (2.38 ± 0.50), were obtained; for Reader 2 the SUVmax ranging from 1.47 to 5.43 (3.20 ± 0.70), SULmean ranging from 0.84 to 3.45 (1.90 ± 0.40), and SULmax ranging from 1.18 to 4.48 (2.38 ± 0.50), were obtained. The coefficient of variance for SUVmax, SULmean, and SULmax, were 21.9%, 21.1%, and 20.8%, respectively, having no significant differences between Reader 1 and Reader 2. The ICC of the two readers for SUVmax, SULmean and SULmax were 0.975, 0.982 and 0.977 (95% CI of 0.97, 0.98 and 0.97; p < .001) respectively. Bland-Altman plots revealed that SUVmax gave the best agreement with 97.1% of measurements falling within 2SD. Conclusion: There is an excellent inter-reader agreement for liver SUVmax, SULmean and SULmax, and the best reliability of measurements achieved with SULmax in contrast-enhanced PET/CT scans