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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.  Analysis of regional bone scan index measurements for the survival of patients with prostate cancer 
BMC Medical Imaging  2014;14:24.
A bone scan is a common method for monitoring bone metastases in patients with advanced prostate cancer. The Bone Scan Index (BSI) measures the tumor burden on the skeleton, expressed as a percentage of the total skeletal mass. Previous studies have shown that BSI is associated with survival of prostate cancer patients. The objective in this study was to investigate to what extent regional BSI measurements, as obtained by an automated method, can improve the survival analysis for advanced prostate cancer.
The automated method for analyzing bone scan images computed BSI values for twelve skeletal regions, in a study population consisting of 1013 patients diagnosed with prostate cancer. In the survival analysis we used the standard Cox proportional hazards model and a more advanced non-linear method based on artificial neural networks. The concordance index (C-index) was used to measure the performance of the models.
A Cox model with age and total BSI obtained a C-index of 70.4%. The best Cox model with regional measurements from Costae, Pelvis, Scapula and the Spine, together with age, got a similar C-index (70.5%). The overall best single skeletal localisation, as measured by the C-index, was Costae. The non-linear model performed equally well as the Cox model, ruling out any significant non-linear interactions among the regional BSI measurements.
The present study showed that the localisation of bone metastases obtained from the bone scans in prostate cancer patients does not improve the performance of the survival models compared to models using the total BSI. However a ranking procedure indicated that some regions are more important than others.
PMCID: PMC4105506  PMID: 25012268
Artificial neural networks; Machine learning; Bone scan index; Survival analysis; Prostate cancer
3.  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
4.  Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: a Japanese multi-center database project 
EJNMMI Research  2013;3:83.
Artificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database.
The BSI was calculated with EXINIbone (EB; EXINI Diagnostics) using the Swedish training database (n = 789). The software using Japanese training databases from a single institution (BONENAVI version 1, BN1, n = 904) and the revised version from nine institutions (version 2, BN2, n = 1,532) were compared. The diagnostic accuracy was validated with another 503 multi-center bone scans including patients with prostate (n = 207), breast (n = 166), and other cancer types. The ANN value (probability of abnormality) and BSI were calculated. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) analyses were performed.
The ROC analysis based on the ANN value showed significant improvement from EB to BN1 and BN2. In men (n = 296), the area under the curve (AUC) was 0.877 for EB, 0.912 for BN1 (p = not significant (ns) vs. EB) and 0.934 for BN2 (p = 0.007 vs. EB). In women (n = 207), the AUC was 0.831 for EB, 0.910 for BN1 (p = 0.016 vs. EB), and 0.932 for BN2 (p < 0.0001 vs. EB). The optimum sensitivity and specificity based on BN2 was 90% and 84% for men and 93% and 85% for women. In patients with prostate cancer, the AUC was equally high with EB, BN1, and BN2 (0.939, 0.949, and 0.957, p = ns). In patients with breast cancer, the AUC was improved from EB (0.847) to BN1 (0.910, p = ns) and BN2 (0.924, p = 0.039). The NRI using ANN between EB and BN1 was 17.7% (p = 0.0042), and that between EB and BN2 was 29.6% (p < 0.0001). With respect to BSI, the NRI analysis showed downward reclassification with total NRI of 31.9% ( p < 0.0001).
In the software for calculating BSI, the multi-institutional database significantly improved identification of bone metastasis compared with the original database, indicating the importance of a sufficient number of training databases including various types of cancers.
PMCID: PMC3877947  PMID: 24369784
Bone scintigraphy; Bone scan index; Artificial neural network; Databases; Multi-center study
5.  Progression of bone metastases in patients with prostate cancer - automated detection of new lesions and calculation of bone scan index 
EJNMMI Research  2013;3:64.
The objective of this study was firstly to develop and evaluate an automated method for the detection of new lesions and changes in bone scan index (BSI) in serial bone scans and secondly to evaluate the prognostic value of the method in a group of patients receiving chemotherapy.
The automated method for detection of new lesions was evaluated in a group of 266 patients using the classifications by three experienced bone scan readers as a gold standard. The prognostic value of the method was assessed in a group of 31 metastatic hormone-refractory prostate cancer patients who were receiving docetaxel. Cox proportional hazards were used to investigate the association between percentage change in BSI, number of new lesions and overall survival. Kaplan-Meier estimates of the survival function were used to indicate a significant difference between patients with an increase/decrease in BSI or those with two or more new lesions or less than two new lesions.
The automated method detected progression defined as two or more new lesions with a sensitivity of 93% and a specificity of 87%. In the treatment group, both BSI changes and the number of new metastases were significantly associated with survival. Two-year survival for patients with increasing and decreasing BSI from baseline to follow-up scans were 18% and 57% (p = 0.03), respectively. Two-year survival for patients fulfilling and not fulfilling the criterion of two or more new lesions was 35% and 38% (n.s.), respectively.
An automated method can be used to calculate the number of new lesions and changes in BSI in serial bone scans. These imaging biomarkers contained prognostic information in a small group of patients with prostate cancer receiving chemotherapy.
PMCID: PMC3751570  PMID: 23947784
Image analysis; Radionuclide imaging; Bone metastases; Prostate cancer; Automated detection; Computer-assisted diagnosis
6.  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
7.  A Novel Automated Platform for Quantifying the Extent of Skeletal Tumour Involvement in Prostate Cancer Patients Using the Bone Scan Index 
European Urology  2012;62(1):78-84.
There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer (PCa), but the popularity of this metric is hampered by the tedium of the manual calculation.
Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features.
Design, setting, and participants
We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained ≤3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements.
The agreement between methods was evaluated using Pearson’s correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index).
Results and limitations
Manual and automated BSI measurements were strongly correlated (ρ = 0.80), correlated more closely (ρ = 0.93) when excluding cases with BSI scores ≥10 (1.8%), and were independently associated with PCa death (p < 0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval [CI], 0.702–0.837) increased to 0.794 (95% CI, 0.727–0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754–0.881) by adding automated BSI scoring to the base model.
Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring.
PMCID: PMC3402084  PMID: 22306323
8.  Improved quantification of small hearts for gated myocardial perfusion imaging 
In patients with a small heart, defined as an end-systolic volume (ESV) of ≤20 mL calculated using the Quantitative Gated SPECT (QGS) program, underestimation of ESV and overestimation of ejection fraction (EF) using gated myocardial perfusion imaging are considered errors caused by inappropriate delineation of the left ventricle (LV). The aim of this study was to develop a new method for delineation of the LV and to evaluate it in studies using a digital phantom, normal subjects and patients.
The active shape-based method for LV delineation, EXINI heart (ExH), was adjusted to more accurately process small hearts. In small hearts, due to the partial volume effect and the short distance to the opposite ventricular wall, the endocardial and the epicardial surfaces are shifted in the epicardial direction depending on the midventricular volume. The adjusted method was evaluated using digital XCAT phantoms with Monte Carlo simulation (8 virtual patients), a Japanese multicentre normal database (69 patients) and consecutive Japanese patients (116 patients). The LV volumes, EF and diastolic parameters derived from ExH and QGS were compared.
The digital phantom studies showed a mean ESV of 87 % ± 9 % of the true volume calculated using ExH and 22 % ± 18 % calculated using QGS. In the normal database, QGS gave higher EFs in women than in men (71.4 ± 6.0 % vs. 67.2 ± 6.0 %, p = 0.0058), but ExH gave comparable EFs (70.7 ± 4.9 % and 71.4 ± 5 % in men and women, respectively, p = ns). QGS gave higher EFs in subjects with a small heart than in those with a normal-sized heart (74.5 ± 5.1 % vs. 66.1 ± 4.9 %), but ExH gave comparable values (70.0 ± 5.9 % vs. 71.6 ± 4.2 %, respectively, p = ns). In consecutive patients, the average EFs with QGS in patients with ESV >20 mL, 11–20 mL and ≤10 mL were 57.9 %, 71.9 % and 83.2 %, but with ExH the differences among these groups were smaller (65.2 %, 67.8 % and 71.5 %, respectively).
The volume-dependent edge correction algorithm was able to effectively reduce the effects on ESV and EF of a small heart. The uniform normal values might be applicable to both men and women and to both small and normal-sized hearts.
PMCID: PMC3699706  PMID: 23632963
Myocardial perfusion imaging; Small heart; Left ventricular function; Software algorithm; Normal values
9.  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
10.  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
11.  Bone Scan Index: a prognostic imaging biomarker for high-risk prostate cancer patients receiving primary hormonal therapy 
EJNMMI Research  2013;3:9.
The objective of this study was to explore the prognostic value of the Bone Scan Index (BSI) obtained at the time of diagnosis in a group of high-risk prostate cancer patients receiving primary hormonal therapy.
This was a retrospective study based on 130 consecutive prostate cancer patients at high risk, based on clinical stage (T2c/T3/T4), Gleason score (8 to 10) and prostate-specific antigen (PSA) (> 20 ng/mL), who had undergone whole-body bone scans < 3 months after diagnosis and who received primary hormonal therapy. BSI was calculated using an automated method. Cox proportional-hazards regression models were used to investigate the association between clinical stage, Gleason score, PSA, BSI and survival. Discrimination between prognostic models was assessed using the concordance index (C-index).
In a multivariate analysis, Gleason score (p = 0.01) and BSI (p < 0.001) were associated with survival, but clinical stage (p = 0.29) and PSA (p = 0.57) were not prognostic. The C-index increased from 0.66 to 0.71 when adding BSI to a model including clinical stage, Gleason score and PSA. The 5-year probability of survival was 55% for patients without metastases, 42% for patients with BSI < 1, 31% for patients with BSI = 1 to 5, and 0% for patients with BSI > 5.
BSI can be used as a complement to PSA to risk-stratify high-risk prostate cancer patients at the time of diagnosis. This imaging biomarker, reflecting the extent of metastatic disease, can be of value both in clinical trials and in patient management when deciding on treatment.
PMCID: PMC3570487  PMID: 23384286
Image analysis; Radionuclide imaging; Bone metastases; Prostate cancer
12.  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
13.  Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database 
Annals of Nuclear Medicine  2012;26(8):622-626.
Computer-aided diagnosis (CAD) software for bone scintigrams have recently been introduced as a clinical quality assurance tool. The purpose of this study was to compare the diagnostic accuracy of two CAD systems, one based on a European and one on a Japanese training database, in a group of bone scans from Japanese patients.
The two CAD software are trained to interpret bone scans using training databases consisting of bone scans with the desired interpretation, metastatic disease or not. One software was trained using 795 bone scans from European patients and the other with 904 bone scans from Japanese patients. The two CAD softwares were evaluated using the same group of 257 Japanese patients, who underwent bone scintigraphy because of suspected metastases of malignant tumors in 2009. The final diagnostic results made by clinicians were used as gold standard.
The Japanese CAD software showed a higher specificity and accuracy compared to the European CAD software [81 vs. 57 % (p < 0.05) and 82 vs. 61 % (p < 0.05), respectively]. The sensitivity was 90 % for the Japanese CAD software and 83 % for the European CAD software (n.s).
The CAD software trained with a Japanese database showed significantly higher performance than the corresponding CAD software trained with a European database for the analysis of bone scans from Japanese patients. These results could at least partly be caused by the physical differences between Japanese and European patients resulting in less influence of attenuation in Japanese patients and possible different judgement of count intensities of hot spots.
PMCID: PMC3475966  PMID: 22729550
Computer-aided diagnosis; Bone scintigram; Bone metastases; Artificial neural networks
14.  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
15.  Semi-automatic analysis of standard uptake values in serial PET/CT studies in patients with lung cancer and lymphoma 
BMC Medical Imaging  2012;12:6.
Changes in maximum standardised uptake values (SUVmax) between serial PET/CT studies are used to determine disease progression or regression in oncologic patients. To measure these changes manually can be time consuming in a clinical routine. A semi-automatic method for calculation of SUVmax in serial PET/CT studies was developed and compared to a conventional manual method. The semi-automatic method first aligns the serial PET/CT studies based on the CT images. Thereafter, the reader selects an abnormal lesion in one of the PET studies. After this manual step, the program automatically detects the corresponding lesion in the other PET study, segments the two lesions and calculates the SUVmax in both studies as well as the difference between the SUVmax values. The results of the semi-automatic analysis were compared to that of a manual SUVmax analysis using a Philips PET/CT workstation. Three readers did the SUVmax readings in both methods. Sixteen patients with lung cancer or lymphoma who had undergone two PET/CT studies were included. There were a total of 26 lesions.
Linear regression analysis of changes in SUVmax show that intercepts and slopes are close to the line of identity for all readers (reader 1: intercept = 1.02, R2 = 0.96; reader 2: intercept = 0.97, R2 = 0.98; reader 3: intercept = 0.99, R2 = 0.98). Manual and semi-automatic method agreed in all cases whether SUVmax had increased or decreased between the serial studies. The average time to measure SUVmax changes in two serial PET/CT examinations was four to five times longer for the manual method compared to the semi-automatic method for all readers (reader 1: 53.7 vs. 10.5 s; reader 2: 27.3 vs. 6.9 s; reader 3: 47.5 vs. 9.5 s; p < 0.001 for all).
Good agreement was shown in assessment of SUVmax changes between manual and semi-automatic method. The semi-automatic analysis was four to five times faster to perform than the manual analysis. These findings show the feasibility of using semi-automatic methods for calculation of SUVmax in clinical routine and encourage further development of programs using this type of methods.
PMCID: PMC3350379  PMID: 22471689
Image analysis; Radionuclide imaging; Quantification
16.  An artificial neural network to safely reduce the number of ambulance ECGs transmitted for physician assessment in a system with prehospital detection of ST elevation myocardial infarction 
Pre-hospital electrocardiogram (ECG) transmission to an expert for interpretation and triage reduces time to acute percutaneous coronary intervention (PCI) in patients with ST elevation Myocardial Infarction (STEMI). In order to detect all STEMI patients, the ECG should be transmitted in all cases of suspected acute cardiac ischemia. The aim of this study was to examine the ability of an artificial neural network (ANN) to safely reduce the number of ECGs transmitted by identifying patients without STEMI and patients not needing acute PCI.
Five hundred and sixty ambulance ECGs transmitted to the coronary care unit (CCU) in routine care were prospectively collected. The ECG interpretation by the ANN was compared with the diagnosis (STEMI or not) and the need for an acute PCI (or not) as determined from the Swedish coronary angiography and angioplasty register. The CCU physician's real time ECG interpretation (STEMI or not) and triage decision (acute PCI or not) were registered for comparison.
The ANN sensitivity, specificity, positive and negative predictive values for STEMI was 95%, 68%, 18% and 99%, respectively, and for a need of acute PCI it was 97%, 68%, 17% and 100%. The area under the ANN's receiver operating characteristics curve for STEMI detection was 0.93 (95% CI 0.89-0.96) and for predicting the need of acute PCI 0.94 (95% CI 0.90-0.97). If ECGs where the ANN did not identify a STEMI or a need of acute PCI were theoretically to be withheld from transmission, the number of ECGs sent to the CCU could have been reduced by 64% without missing any case with STEMI or a need of immediate PCI.
Our ANN had an excellent ability to predict STEMI and the need of acute PCI in ambulance ECGs, and has a potential to safely reduce the number of ECG transmitted to the CCU by almost two thirds.
PMCID: PMC3293011  PMID: 22296816
17.  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
18.  Diagnostic evaluation of three cardiac software packages using a consecutive group of patients 
EJNMMI Research  2011;1:22.
The aim of this study was to compare the diagnostic performance of the three software packages 4DMSPECT (4DM), Emory Cardiac Toolbox (ECTb), and Cedars Quantitative Perfusion SPECT (QPS) for quantification of myocardial perfusion scintigram (MPS) using a large group of consecutive patients.
We studied 1,052 consecutive patients who underwent 2-day stress/rest 99mTc-sestamibi MPS studies. The reference/gold-standard classifications for the MPS studies were obtained from three physicians, with more than 25 years each of experience in nuclear cardiology, who re-evaluated all MPS images. Automatic processing was carried out using 4DM, ECTb, and QPS software packages. Total stress defect extent (TDE) and summed stress score (SSS) based on a 17-segment model were obtained from the software packages. Receiver-operating characteristic (ROC) analysis was performed.
A total of 734 patients were classified as normal and the remaining 318 were classified as having infarction and/or ischemia. The performance of the software packages calculated as the area under the SSS ROC curve were 0.87 for 4DM, 0.80 for QPS, and 0.76 for ECTb (QPS vs. ECTb p = 0.03; other differences p < 0.0001). The area under the TDE ROC curve were 0.87 for 4DM, 0.82 for QPS, and 0.76 for ECTb (QPS vs. ECTb p = 0.0005; other differences p < 0.0001).
There are considerable differences in performance between the three software packages with 4DM showing the best performance and ECTb the worst. These differences in performance should be taken in consideration when software packages are used in clinical routine or in clinical studies.
PMCID: PMC3250995  PMID: 22214226
myocardial perfusion imaging; SPECT; automatic quantification; software; coronary artery disease
19.  Asymmetric Cerebral Blood Flow in Patients with Mild Cognitive Impairment: Possible Relationship to Further Cognitive Deterioration 
To explore patterns of cerebral blood flow in patients with mild cognitive impairment (MCI), who (1) eventually deteriorate into overt dementia, with no particular focus on the type of dementia, or (2) do not appear to further deteriorate in their cognitive functions.
Thirty-seven MCI patients, with or without vascular pathology, were studied prospectively. The patients underwent 99mTc-HMPAO SPECT analysis at baseline. Possible clinical conversion into dementia within a 2-year period was assessed.
Nineteen patients had progressive MCI (PMCI), while 18 patients were considered clinically stable (SMCI). PMCI patients had more often abnormally low cerebral blood flow in at least one of the frontal, temporal, parietal or occipital lobes compared to SMCI patients (12/19 vs. 5/18; p = 0.049). At least one of the temporal regions was found to be abnormal in 9 PMCI patients in contrast to only 1 SMCI patient (p = 0.008). More specifically, blood flow in the medial portion of the left temporal region was abnormal in 8 PMCI patients, a pattern seen in 1 SMCI patient only (p = 0.019).
The results suggest that blood flow reductions particularly in the left medial temporal region indicate an elevated risk of further cognitive decline in MCI patients.
PMCID: PMC3199881  PMID: 22163247
Cerebral blood flow; Cognitive decline; Mild cognitive impairment; Progressive dementia; SPECT
20.  Normal limits for left ventricular ejection fraction and volumes determined by gated single photon emission computed tomography – a comparison between two quantification methods 
To compare gender-related normal limits for left ventricular (LV) ejection fraction (EF), end-diastolic and end-systolic volumes (EDV and ESV), obtained using two myocardial perfusion-gated single photon emission computed tomography (SPECT) quantification methods. A total of 185 patients were retrospectively selected from a consecutive series of patients examined for coronary artery disease (CAD) or for management of known CAD. Patients were included in the study group if they had normal or probably normal results with stress and rest perfusion imaging and if the combined interpretation of perfusion studies and gated rest studies showed no signs or suspicion of myocardial infarction. The gated SPECT studies were performed using a 2-day stress/gated rest Tc-99m sestamibi protocol. All patient studies were processed using CAFU and quantitative-gated SPECT (QGS), the two software packages for quantification of gated SPECT images. The lower normal limits for EF were higher for CAFU compared with QGS for both women (59% versus 53%) and men (54% versus 47%). The upper normal limits for EDV were also higher for CAFU compared with QGS for both women (133 versus 107 ml) and men (182 versus 161 ml). The differences between the software packages were small for ESV (women 44 versus 44 ml; men 69 versus 74 ml). Gender-specific normal limits need to be applied for LV EF and volumes determined by gated SPECT. Separate criteria for abnormal LV EF and EDV need to be used for women and men depending on the software package used.
PMCID: PMC2442753  PMID: 18312447
computer-assisted; gender; heart function tests; radionuclide imaging; reference values
21.  A simple statistical model for prediction of acute coronary syndrome in chest pain patients in the emergency department 
Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED.
Multivariable analysis and logistic regression were used on data from 634 ED visits for chest pain. Only data immediately available at patient presentation were used. To make ACS prediction stable and the model useful for personnel inexperienced in electrocardiogram (ECG) reading, simple ECG data suitable for computerized reading were included.
Besides ECG, eight variables were found to be important for ACS prediction, and included in the model: age, chest discomfort at presentation, symptom duration and previous hypertension, angina pectoris, AMI, congestive heart failure or PCI/CABG. At an ACS prevalence of 21% and a set sensitivity of 95%, the negative predictive value of the model was 96%.
The present prediction model, combined with the clinical judgment of ED personnel, could be useful for the early discharge of chest pain patients in populations with a low prevalence of ACS.
PMCID: PMC1559601  PMID: 16824205
22.  Direct hospital costs of chest pain patients attending the emergency department: a retrospective study 
Chest pain is one of the most common complaints in the Emergency Department (ED), but the cost of ED chest pain patients is unclear. The aim of this study was to describe the direct hospital costs for unselected chest pain patients attending the emergency department (ED).
1,000 consecutive ED visits of patients with chest pain were retrospectively included. Costs directly following the ED visit were retrieved from the hospital economy system.
The mean cost per patient visit was 26.8 thousand Swedish kronar (kSEK) (median 7.2 kSEK), with admission time accounting for 73% of all costs. Mean cost for patients discharged from the ED was 1.4 kSEK (median 1.3 kSEK), and for patients without ACS admitted 1 day or less 7.6 kSEK (median 6.9 kSEK). The practice in the present study to admit 67% of the patients, of whom only 31% proved to have ACS, was estimated to give a cost per additional life-year saved by hospital admission, compared to theoretical strategy of discharging all patients home, of about 350 kSEK (39 kEUR or 42 kUSD).
Costs for chest pain patients are large and primarily due to admission time. The present admission practice seems to be cost-effective, but the substantial overadmission indicates that better ED diagnostics and triage could decrease costs considerably.
PMCID: PMC1488872  PMID: 16674827
23.  A new automated method for analysis of rCBF-SPECT images based on the active-shape algorithm: normal values 
Most nuclear medicine clinicians use only visual assessment when interpreting regional cerebral blood flow (rCBF) from single-photon emission computed tomography (SPECT) images in clinical practice. The aims of this study were to develop a new, easy to use, automated method for quantification of rCBF-SPECT and to create normal values by using the method on a normal population. We developed a 3-dimensional method based on a brain-shaped model and the active-shape algorithm. The method defines the surface shape of the brain and then projects the maximum counts 0–1·5 cm deep for designated surface points. These surface projection values are divided into cortical regions representing the different lobes and presented relative to the whole cortex, cerebellum or cerebellar maximum. 99mTc-hexa methyl propylene amine oxime (HMPAO) SPECT was performed on 30 healthy volunteers with a mean age of 74 years (range 64–98). The ability of the active-shape algorithm to define the shape of the brain was satisfactory when visually scrutinized. The results of the quantification show rCBF values in the frontal, temporal and parietal lobes of 87–88% using cerebellum as the reference. There were no significant differences in normal rCBF values between male and female subjects and only a weak relation between rCBF and age. In conclusion, our new automated method was able to quantify rCBF-SPECT images and create normal values in ranges as expected. Further studies are needed to assess the clinical value of this method and the normal values.
PMCID: PMC3440586  PMID: 22296631
active shape; image processing; normal values; quantification; radionuclide imaging; regional cerebral blood flow; single-photon emission computed tomography

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