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1.  Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy 
EJNMMI Research  2014;4:58.
Bone Scan Index (BSI) is a quantitative measurement of tumour burden in the skeleton calculated from bone scan images. When analysed at the time of diagnosis, it has been shown to provide prognostic information on survival in men with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic value of BSI during androgen deprivation therapy (ADT).
Prostate cancer patients who were at high risk of a poor outcome and who had undergone bone scan at the time of diagnosis and during ADT were recruited from two university hospitals for a retrospective study. BSI at baseline and follow-up were calculated using an automated software package (EXINIbonebsi). Associations between BSI, other prognostic biomarkers and overall survival (OS) were evaluated using a Cox proportional hazards regression model.
One hundred forty-six PCa patients were included in the study. A total of 102 patient deaths were registered, with a median survival time after the follow-up bone scan of 2.4 years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT, BSI was significantly associated with OS in univariate and multivariate analyses. When BSI was added to a prognostic base model including age, prostate-specific antigen, clinical tumour stage and Gleason score, the concordance index increased from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001) during ADT.
Automated BSI during ADT is an independent prognostic indicator of OS in PCa patients with bone metastasis. It represents an emerging imaging biomarker that can be used in a prognostic model for risk stratification of PCa patients at the time of diagnosis and at later stages of the disease. BSI could then help physicians identify patients who could benefit from more aggressive therapies.
PMCID: PMC4205473  PMID: 25386390
Prostate cancer; Bone Scan Index; Androgen deprivation therapy; Bone metastases
2.  Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams 
BMC Medical Imaging  2014;14:5.
The European Society of Cardiology recommends that patients with >10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects.
Twenty-five myocardial perfusion single photon emission computed tomography (SPECT) patients who were regarded as ischemic according to the final report were included. Eleven physicians in nuclear medicine delineated the extent of the ischemic defects. After at least two weeks, they delineated the defects again, and were this time provided a suggestion of the defect delineation by EXINI HeartTM (EXINI). Summed difference scores and ischemic extent values were obtained from four software programs.
The median extent values obtained from the 11 physicians varied between 8% and 34%, and between 9% and 16% for the software programs. For all 25 patients, mean extent obtained from EXINI was 17.0% (± standard deviation (SD) 14.6%). Mean extent for physicians was 22.6% (± 15.6%) for the first delineation and 19.1% (± 14.9%) for the evaluation where they were provided computerized suggestion. Intra-class correlation (ICC) increased from 0.56 (95% confidence interval (CI) 0.41-0.72) to 0.81 (95% CI 0.71-0.90) between the first and the second delineation, and SD between physicians were 7.8 (first) and 5.9 (second delineation).
There was large variability in the estimated ischemic defect size obtained both from different physicians and from different software packages. When the physicians were provided with a suggested delineation, the inter-observer variability decreased significantly.
PMCID: PMC3922637  PMID: 24479846
Ischemic heart disease; Myocardial perfusion imaging; Intra-observer variability; Software tools
3.  Prognosis of patients without perfusion defects with and without rest study in myocardial perfusion scintigraphy 
EJNMMI Research  2013;3:58.
Stress myocardial perfusion scintigraphy (MPS) is widely regarded as a useful imaging modality for diagnosing patients with suspected ischemic heart disease. Current European guidelines recommend stress study to be performed first since rest study can be omitted if stress study is interpreted as normal. Thus, a rest study should only be performed in patients with equivocal or abnormal studies. The aim of the present study was to investigate the prognosis of a normal stress-only MPS compared to a normal stress-rest MPS in a retrospective manner and also with regard to normal/abnormal left ventricular function data.
All 4,820 patients who underwent 99mTc MPS at Skåne University Hospital in Malmö, Sweden, in 2004 to 2007, for suspected or management of known ischemic heart disease were considered. The physician in clinical charge of the investigation decided whether a rest study was necessary or not. Based on the final report according to clinical routine, only patients with a normal perfusion study (no infarction or inducible ischemia) were included. The endpoints were non-fatal acute coronary syndrome or death from ischemic cardiac origin.
A total of 3,426 patients with a normal perfusion study were included. Of these, 2,215 patients had a stress-only study and 1,211 patients had both stress and rest studies. Mean follow-up was 6.2 years. The lowest event rate was found in the normal stress-only group (0.56% for normal stress-only patients vs. 1.42% for normal stress-rest patients; p < 0.0001). When dividing patients according to sex and stress type, the best prognosis was also found in the normal stress-only group (p < 0.0001 for all comparisons). Regarding left ventricular function data, we did not find any significant difference in event rate between normal vs. abnormal ejection fraction (EF), normal vs. abnormal end-diastolic volume (EDV) or normal EF, and EDV vs. abnormal EF or EDV for either the normal stress-only patients or the normal stress-rest patients.
Patients with a normal stress-only study had an excellent prognosis over a mean follow-up time of 6 years. Thus, omitting the rest study if the stress study is normal is a safe procedure.
PMCID: PMC3733807  PMID: 23902737
Myocardial perfusion imaging; Ischemic heart disease; Prognostic value
4.  Adding attenuation corrected images in myocardial perfusion imaging reduces the need for a rest study 
BMC Medical Imaging  2013;13:14.
The American Society of Nuclear Cardiology and the Society of Nuclear Medicine conclude that incorporation of attenuation corrected (AC) images in myocardial perfusion scintigraphy (MPS) will improve diagnostic accuracy. The aim was to investigate the value of adding AC stress-only images for the decision whether a rest study is necessary or not.
1,261 patients admitted to 99mTc MPS were studied. The stress studies were interpreted by two physicians who judged each study as “no rest study necessary” or “rest study necessary”, by evaluating NC stress-only and NC + AC stress-only images. When there was disagreement between the two physicians, a third physician evaluated the studies. Thus, agreement between 2 out of 3 physicians was evaluated.
The physicians assessed 214 more NC + AC images than NC images as “no rest study necessary” (17% of the study population). The number of no-rest-study-required was significantly higher for NC + AC studies compared to NC studies (859 vs 645 cases (p < 0.0001). In the final report according to clinical routine, ischemia or infarction was reported in 23 patients, assessed as “no rest study necessary” (22 NC + AC cases; 8 NC cases), (no statistically significant difference). In 11 of these, the final report stated “suspected/possible ischemia or infarction in a small area”.
Adding AC stress-only images to NC stress-only images reduce the number of unnecessary rest studies substantially.
PMCID: PMC3618204  PMID: 23547878
Tc99m MPS; Ischemic cardiac disease; Attenuation correction; Stress-only studies
5.  When is reacquisition necessary due to high extra-cardiac uptake in myocardial perfusion scintigraphy? 
EJNMMI Research  2013;3:20.
Technetium-labeled agents, which are most often used for assessing myocardial perfusion in myocardial perfusion scintigraphy (MPS), are cleared by the liver and excreted by the biliary system. Spillover from extra-cardiac activity into the myocardium, especially the inferior wall, might conceal defects and lower the diagnostic accuracy of the study. The objective was to determine rules of thumb for when reacquisition is useful due to high extra-cardiac uptake, i.e., when interpretation of the studies was affected by poor image quality.
Patients admitted to MPS at any of the three study sites, who also underwent a reacquisition due to high extra-cardiac uptake were included. Image quality was assessed by ten technologists on a scale ranging from 1 to 5. Interpretations regarding the presence/absence of ischemia/infarction, including the certainty of the diagnosis, were made by three physicians.
There was a statistically significant increase in image quality between the first and the repeated acquisition (1,256 cases of increased quality at the repeated study (66%), 134 cases of decreased quality at the repeated study (7%), 510 cases of unchanged quality (27%) P < 0.0001). The number of equivocal studies, interpreted by physicians, decreased when evaluating the repeated studies compared to the first studies for all physicians, both for the interpretations of ischemia and for infarction. Receiver operating characteristic analyses revealed that for both endpoints (ischemia, infarction) and all physicians, the optimal cutoff point for performing a reacquisition was between quality categories 2 and 3.
This study indicates that repeat acquisition is useful when (1) the intensity of the extra-cardiac uptake is equal to or higher than the cardiac uptake when there is no separation between the extra-cardiac uptake and the inferior cardiac wall and (2) when the intensity of the extra-cardiac uptake is higher than the cardiac uptake when there is a separation between the extra-cardiac uptake and the inferior wall of less than one cardiac wall.
PMCID: PMC3614539  PMID: 23521849
Myocardial perfusion imaging; Quality assessment; Image interpretation; Extra-cardiac uptake; Ischemic heart disease
6.  Nuclear medicine technologists are able to accurately determine when a myocardial perfusion rest study is necessary 
In myocardial perfusion scintigraphy (MPS), typically a stress and a rest study is performed. If the stress study is considered normal, there is no need for a subsequent rest study. The aim of the study was to determine whether nuclear medicine technologists are able to assess the necessity of a rest study.
Gated MPS using a 2-day 99mTc protocol for 121 consecutive patients were studied. Visual interpretation by 3 physicians was used as gold standard for determining the need for a rest study based on the stress images. All nuclear medicine technologists performing MPS had to review 82 training cases of stress MPS images with comments regarding the need for rest studies, and thereafter a test consisting of 20 stress MPS images. After passing this test, the nuclear medicine technologists in charge of a stress MPS study assessed whether a rest study was needed or not or if he/she was uncertain and wanted to consult a physician. After that, the physician in charge interpreted the images and decided whether a rest study was required or not.
The nuclear medicine technologists and the physicians in clinical routine agreed in 103 of the 107 cases (96%) for which the technologists felt certain regarding the need for a rest study. In the remaining 14 cases the technologists were uncertain, i.e. wanted to consult a physician. The agreement between the technologists and the physicians in clinical routine was very good, resulting in a kappa value of 0.92. There was no statistically significant difference in the evaluations made by technicians and physicians (P = 0.617).
The nuclear medicine technologists were able to accurately determine whether a rest study was necessary. There was very good agreement between nuclear medicine technologists and physicians in the assessment of the need for a rest study. If the technologists can make this decision, the effectiveness of the nuclear medicine department will improve.
PMCID: PMC3457849  PMID: 22947251
Image interpretation; Radionuclide imaging; Ischemic heart disease; 99Tc MPS
7.  Referring physicians underestimate the extent of abnormalities in final reports from myocardial perfusion imaging 
EJNMMI Research  2012;2:27.
It is important that referring physicians and other treating clinicians properly understand the final reports from diagnostic tests. The aim of the study was to investigate whether referring physicians interpret a final report for a myocardial perfusion scintigraphy (MPS) test in the same way that the reading nuclear medicine physician intended.
After viewing final reports containing only typical clinical verbiage and images, physicians in nuclear medicine and referring physicians (physicians in cardiology, internal medicine, and general practitioners) independently classified 60 MPS tests for the presence versus absence of ischemia/infarction according to objective grades of 1–5 (1 = No ischemia/infarction, 2 = Probably no ischemia/infarction 3 = Equivocal, 4 = Probable ischemia/infarction, and 5 = Certain ischemia/infarction). When ischemia and/or infarction were thought to be present in the left ventricle, all physicians were also asked to mark the involved segments based on the 17-segment model.
There was good diagnostic agreement between physicians in nuclear medicine and referring physicians when assessing the general presence versus absence of both ischemia and infarction (median squared kappa coefficient of 0.92 for both). However, when using the 17-segment model, compared to the physicians in nuclear medicine, 12 of 23 referring physicians underestimated the extent of ischemic area while 6 underestimated and 1 overestimated the extent of infarcted area.
Whereas referring physicians gain a good understanding of the general presence versus absence of ischemia and infarction from MPS test reports, they often underestimate the extent of any ischemic or infarcted areas. This may have adverse clinical consequences and thus the language in final reports from MPS tests might be further improved and standardized.
PMCID: PMC3466153  PMID: 22682066
Structured reporting; Ischemic heart disease; 99mTc MPS; Infarction; Ischemia
8.  Small average differences in attenuation corrected images between men and women in myocardial perfusion scintigraphy: a novel normal stress database 
BMC Medical Imaging  2011;11:18.
The American Society of Nuclear Cardiology and the Society of Nuclear Medicine state that incorporation of attenuation-corrected (AC) images in myocardial perfusion scintigraphy (MPS) will improve image quality, interpretive certainty, and diagnostic accuracy. However, commonly used software packages for MPS usually include normal stress databases for non-attenuation corrected (NC) images but not for attenuation-corrected (AC) images. The aim of the study was to develop and compare different normal stress databases for MPS in relation to NC vs. AC images, male vs. female gender, and presence vs. absence of obesity. The principal hypothesis was that differences in mean count values between men and women would be smaller with AC than NC images, thereby allowing for construction and use of gender-independent AC stress database.
Normal stress perfusion databases were developed with data from 126 male and 205 female patients with normal MPS. The following comparisons were performed for all patients and separately for normal weight vs. obese patients: men vs. women for AC; men vs. women for NC; AC vs. NC for men; and AC vs. NC for women.
When comparing AC for men vs. women, only minor differences in mean count values were observed, and there were no differences for normal weight vs. obese patients. For all other analyses major differences were found, particularly for the inferior wall.
The results support the hypothesis that it is possible to use not only gender independent but also weight independent AC stress databases.
PMCID: PMC3205014  PMID: 21967548

Results 1-8 (8)