F. I. McKiddie

Determination of normal regional left ventricular function from cine-MR images using a semi-automated edge detection method

A semi-automated edge detection method for the delineation of the endo- and epicardial borders of the left ventricle from cine MR images has been developed. The feasibility of this was demonstrated by processing end diastolic and end systolic ECG-gated images of four short axis images in 10 healthy subjects. The first derivative method combined with a 2D weighted polynomial fitting procedure was used to determine the endo- and epicardial borders, which then allowed determination of the wall motion, wall thickening, and ejection fraction, of the left ventricle. The results show that the end-systolic radial wall motion varies from (32+/-8)% to (76+/-12)%, and wall thickening from (0.60+/-0.46) cm to (1.26+/-0.50) cm. An average ejection fraction of (69+/-6)% was found which agrees well with literature values. The method described, for the delineation of the borders, reduces considerably the long and tedious operator time inherent in manual measurement and greatly increases the reproducibility of the measurements.

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Background:Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy.Methods:Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations.Results:We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin.Conclusions:In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

Automatic detection of coronary artery disease in myocardial perfusion SPECT using image registration and voxel to voxel statistical comparisons

The purpose of this study was to compare the performance of automatic detection of coronary artery disease (CAD) with that of expert observers. A male and female normal image template was constructed from normal stress technetium-99m single photon emission computed tomography (SPECT) studies. Mean and standard deviation images for each sex were created by registering normal studies to a standard shape and position. The test group consisted of 104 patients who had been routinely referred for SPECT and angiography. The gold standard for CAD was defined by angiography. The test group studies were registered to the respective templates and the Z-score was calculated for each voxel. Voxels with a Z-score greater than 5 indicated the presence of CAD. The performance of this method and that of three observers were compared by continuous receiver operating characteristic (CROC) analysis. The overall sensitivity and specificity for automatic detection were 73% and 92%, respectively. The area (Az) under the CROC curve (±1 SE) for automatic detection of CAD was 0.88±0.06. There was no statistically significant difference between the performances of the three observers in terms of Az and that of automatic detection (P⩾0.25, univariate Z-score test). The use of this automated statistical mapping approach shows a performance comparable with experienced observers, but avoids inter-observer and intra-observer variability.

Comparison of methods for quantification of transient ischaemic dilation in myocardial perfusion SPET.

The purpose of this study was to compare six methods of measuring the left ventricular (LV) transient ischaemic dilation (TID) ratio during stress-rest myocardial perfusion single-photon emission tomography (SPET). The TID ratio was defined as the mean LV short-axis area at stress divided by the mean LV area of similar slices at rest. The centre of the LV wall was defined as either the maximum, mean or median of the radial short-axis count profiles. The area within the endocardial wall was also calculated for each definition of the LV wall centre. We identified 50 consecutive patients undergoing dipyridamole technetium-99m-tetrofosmin SPET imaging and angiography. Continuous receiver operating characteristic (CROC) analysis showed no significant difference between the six methods in terms of identifying severe coronary artery disease (P>0.47). Algorithms using the mean or the median value in the profile were significantly more robust than those using the maximum (P<0.0005). TID measured by all the algorithms is an indicator of severe coronary disease (P<0.05). The algorithms compared provide a repeatable, quantitative and specific measure of the TID ratio.

Sehcat retention values as measured with a collimated and an uncollimated gamma camera: a method comparison study

TauroH-23-(75Se) selena-25-homocholic acid retention values are used in the diagnosis of bile acid malabsorption. The standard method for measuring values is with an uncollimated gamma camera, which can create some logistic difficulties, with other background sources of activity, which are irrelevant when a collimator is used, becoming significant. In this study we compare the retention values obtained with a collimated and an uncollimated gamma camera in phantoms and in 23 patients. Bland–Altman plots were created using the data, which showed a mean bias in retention of 0.10% in the phantom study and 0.55% in the patient study between methods. A Wilcoxon signed-rank test with the null hypothesis of zero median difference between uncollimated and collimated methods was not statistically significant to P values less than 0.05 in the patient and phantom studies. In the patient study, on using a fixed boundary of retention (10%) between positive and negative status, the status of one patient was changed from negative (12%) to positive (9%). We conclude that measurement of retention with a collimated gamma camera is similar but not identical to that of uncollimated values. The clinical significance of this shift is unclear, as the threshold of significance and the method of integrating this measure with other clinical factors into management remain unclear.

Improvement in DMSA imaging using adaptive noise reduction: an ROC analysis.

Dimercaptosuccinic acid imaging is the ‘gold standard’ for the detection of cortical defects and diagnosis of scarring of the kidneys. The Siemens planar processing package, which implements adaptive noise reduction using the Pixon algorithm, is designed to allow a reduction in image noise, enabling improved image quality and reduced acquisition time/injected activity. This study aimed to establish the level of improvement in image quality achievable using this algorithm. Images were acquired of a phantom simulating a single kidney with a range of defects of varying sizes, positions and contrasts. These images were processed using the Pixon processing software and shown to 12 observers (six experienced and six novices) who were asked to rate the images on a six-point scale depending on their confidence that a defect was present. The data were analysed using a receiver operating characteristic approach. Results showed that processed images significantly improved the performance of the experienced observers in terms of their sensitivity and specificity. Although novice observers showed significant increase in sensitivity when using the software, a significant decrease in specificity was also seen. This study concludes that the Pixon software can be used to improve the assessment of cortical defects in dimercaptosuccinic acid imaging by suitably trained observers.

An assessment of perfusion deficits in decompression illness using 99Tcm HMPAO SPET and statistical parametric mapping

Aim The aim of this study was to use statistical parametric mapping (SPM) to investigate differences in the regional cerebral blood flow (rCBF) of decompression illness (DCI) and non-diving control subjects. Methods Twenty DCI subjects were imaged using 99Tcm hexamethylproplylene amine oxime (HMPAO) single photon emission tomography (SPET) within days of their incident of DCI, and on a second occasion between 2 and 27 months after their DCI event. SPM was used to make a comparison between decompression illness studies and a second group of non-diving control studies for both early and late imaging of DCI. A paired comparison of early and late imaging was also performed testing for correlation between time of imaging and changes in the rCBF pattern. Results The comparison between control subjects and early imaging of decompression illness showed a large, significant (P = 0.002), irregularly shaped, multi-focal area of reduced uptake in the left occipito-parieto-temporal region of the brain. Comparisons between control and repeat decompression illness imaging studies showed two areas of reduced uptake. The first was similar to that found in the initial comparison although it was less significant (P = 0.035). The second region was similar but contra-lateral to the first region with significance P<0.001. An attempt to correlate any changes in rCBF with the time that elapsed between each set of imaging found no areas of significant correlation. Conclusion 99Tcm HMPAO SPET images of decompression illness display areas of reduced perfusion, which persist in the majority of cases.

A variable threshold edge-detector for improved quantitation of gated tomographic imaging of the left ventricular blood pool

SummaryThe accurate measurement of left ventricular volume from tomographic MUGA studies is difficult due to the limited resolving power of the gamma camera, which causes errors in the detection of the correct ventricular boundaries. Therefore, the use of fixed threshold or second-derivative edge-detectors results in overestimates at small volumes. A variable threshold edge-detection technique was developed to overcome this. Computer-simulated short-axis slices through the heart over a range of left ventricular dimensions were convolved by the Point Spread Response Function of the system to model the acquired image. The maximum pixel value and the threshold value required to detect the true ventricular edge from each simulation were then combined into a look-up table for the calculation of the required threshold value. As the dimension of the ventricle decreased, the threshold value chosen to detect the ventricular edge increased. Left ventricular volumes and ejection fraction measurements were calculated for seven patients using cine-MRI as the gold-standard technique for validation of the proposed method. The single photon emission tomographic studies were analysed using both the standard second-derivative edge-detection software and the proposed variable threshold technique. The variable threshold technique was shown to increase significantly the accuracy of ventricular volume measurements and ejection fraction calculations. The average error in the measurement of volumes was reduced from 41.4 ± 45.1% to 18.5 ± 14.6% and the accuracy of ejection fraction measurement was increased from 29.7 ± 4.6% to 11.3 ± 6.9%.

The impact of cell labelling technique on the retention of indium-labelled platelet imaging for idiopathic thrombocytopenic purpura.

Indium-labelled autologous platelet imaging is a nuclear imaging technique in which autologous platelets are reinfused into the patient after in-vitro labelling with indium-111. Subsequent scintigraphy demonstrates and quantifies sites of platelet sequestration and clearance. It is recommended for the assessment of patients being considered for splenectomy [1] and has shown utility as an adjunct predictive instrument before splenectomy [2]. Our reason for writing is to share our experience of switching from an indium-oxine-labelling technique to an indium-tropolone technique [3]. This change was forced upon us by the withdrawal of indium-oxine from the EU market in 2013 (GE Healthcare customer communication 21 March 2013). As part of our quality assurance procedures we reviewed hepatic and splenic retention ratios for patients who underwent indium-111-labelled platelet reinfusion examinations. In this review we examined two groups of patients: 11 who had platelets labelled with indium-oxine and 13 labelled with indium-tropolone. The two groups were not different in terms of age, sex, and disease status. The majority of patients were referred from the same referral team within NHS-Grampian. Our imaging protocol consisted of imaging over 5 days, and the ratio of the liver and spleen count on days 1–4 to that on day 0 was calculated. The liver and spleen count was calculated by the geometric mean method using a fixed region of interest for the anterior and posterior views. The images were manually registered if required between days. The results are shown in Fig. 1, with each line representing a single patient.

The suitability of gamma camera coincidence systems for nitrogen 13-labeled ammonia myocardial perfusion imaging: a quantitative comparison with full-ring PET.

BackgroundThe aim of this study was to examine the quality of nitrogen 13-labeled ammonia (NH3) perfusion data from coincidence-capable gamma camera positron emission tomography (GC-PET) systems compared with that from full-ring positron emission tomography (FR-PET).Methods and ResultsThe performance parameters of the GC-PET system were examined and found adequate for imaging at the activity levels used clinically. We studied 15 patients who underwent stress and rest N-13-labeled NH3 perfusion imaging on FR-PET and GC-PET systems. Quantitative analysis of perfusion values showed that GC-PET uptake was significantly lower than FR-PET uptake in 67.6% of segments. Bland-Altman analysis showed that the mean difference between FR-PET and GC-PET values was from 5.3% to 5.9%. Stress FR-PET identified 49 segments as having impaired perfusion, 46 (93.9%) of which were also identified by GC-PET. Fifty-six additional segments were identified as abnormal by GC-PET. These findings indicated a general overestimation of defect size on GC-PET. Analysis of the degree of perfusion reduction also found that GC-PET tended to overestimate defect contrast. These findings are similar to those previously found by workers examining fluorine 18-fluorodeoxyglucose uptake by both techniques.ConclusionsGood concordance was shown between GC-PET and FR-PET systems for N-13-labeled NH3 perfusion imaging, although further work is required to optimize the technique.