Department of Medical Imaging and Clinical Oncology
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- ItemThe added value of SPECT/CT in complicated osteomyelitis(Stellenbosch : Stellenbosch University, 2013-12) Tag, Naima; Korowlay, Nisaar A.ENGLISH ABSTRACT: Background: The detection of bone infection can be very difficult especially in bone with altered structure due to prior trauma or surgical procedures. Complicated osteomyelitis (COM) is becoming a public health problem especially with the difficult choice between, high cost surgery and prolonged courses of intravenous or oral antibiotic therapy, as well as the social and psychological effect of longterm disease and disability of the patient. The correct localisation of especially bone infection is still a challenge for the clinician. The single photon emission computed tomography/low dose computed tomography (SPECT/CT), by fusing the functional information with the anatomical parts, is a wellestablished tool used in many nuclear medicine studies. This improves the overall quality of the study with more clear answers. The aim of the study was to determine the added value of SPECT/CT in the management of complicated osteomyelitis (COM) in patients with endo-prosthesis, post traumatic osteomyelitis with and without metal implants and diabetic foot. Methods: This was a prospective study, between February 2010 and February 2012. Patients with suspected COM who fulfilled the selection and inclusion criteria were included. All had abnormal three phase bone scan followed by infection imaging with 99mTc labelled white blood cells and 99mTc -colloid if the99mTc labelled white blood cell study was abnormal. 67Ga citrate was used in vertebral involvement. Planar and SPECT/CT images were reviewed for presence of abnormal uptake and for its localization in bone and soft tissue. Scan results were defined as positive or negative. Both planar and SPECT/CT images were compared regarding diagnosis and precise localization of infection. The final diagnosis was obtained from surgical specimen or microbiological culture as well as clinical follow-up of all patients. Results: There were 72 patients, 29 male and 43 female with mean age of 57 yrs [range 27-88].There were 24 patients with prosthesis, 16 with hip prosthesis (PH=16), and 8 with knee prosthesis (PK=8). There were 44 patients with post traumatic osteomyelitis, 26 with metal implants (TOM=26) and 18 without metal implants (TOWM= 18). Four patients had diabetic foot (DF= 4). Infection was diagnosed in 19/72 patients on planar images and in 21/72 on SPECT/CT. Infection was diagnosed in 4 patients with prosthesis, 16 patients with post traumatic injury and one diabetic foot patient. The four patients with prosthesis, SPECT /CT added diagnostic value by excluding osteomyelitis in 3 patients and by defining the exact extent and localizing soft tissue and bone infection (STI/OM) in one patient. In 16 patients with post traumatic OM on planar images, SPECT /CT added diagnostic value, by excluding OM in 4 patients and confirming only STI, better localisation of the uptake in bone and soft tissue in 5 patients, of them 2 patient was negative on planar, and in 7 patients, confirmed and defined the exact extent of both OM and STI. One diabetic foot was positive for STI on the planar, the SPECT/CT added diagnostic value by defining the extent of the infection. In summary the added value of SPECT/CT was: a. Overall infection: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (10%) 2. Better localization in bone and soft tissue: 6 patients (8%) 3. Better delineation of extent of infection: 9 patients (12%) 4. None: 50 patients (70%) b. In positive cases only: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (33%) 2. Better localization in bone and soft tissue: 5 patients (24%) 3. Better delineation of extent of infection: 9 patients (43%) 4. None: 0 patients The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy for infection, on planar was 90%, 100%, 100%, 97%, 97%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. For OM on planar, the sensitivity, specificity , positive predictive value, negative predictive value and accuracy was 100%, 89%, 53%, 100%, 90%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. Conclusion: In complicated osteomyelitis, SPECT/CT is useful in localizing, defining the exact extent of infection where the planar images are abnormal, with no added value if the planar images are negative. We recommend in clinical practice the routine use of hybrid SPECT/CT imaging in complicated osteomyelitis when planar images are abnormal.
- ItemThe added value of SPECT/CT in the evaluation of equivocal skeletal lesions in patients with known malignant disease(Stellenbosch : University of Stellenbosch, 2010-03) Ndlovu, Xolani; Warwick, James M.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY: Introduction: Bone scintigraphy is used extensively in evaluating metastatic disease. There are currently no clear recommendations for the use of SPECT/CT in metastatic bone disease. Existing procedural guidelines from the Society of Nuclear Medicine (SNM) for SPECT/CT do not provide specific indications for use of SPECT/CT in bone scintigraphy, and there are currently no other guidelines for the use of SPECT/CT in bone scintigraphy that the author is aware of. The aim of this study was to investigate the additional value of SPECT/CT, and to identify the clinical indications for which SPECT/CT is most useful in patients with suspected bone metastases. Subjects and Methods: Forty-two patients with equivocal lesions on planar scintigraphy were prospectively recruited and planar imaging, SPECT, and SPECT/CT done on all patients. On reading of SPECT and then SPECT/CT, patients and individual lesions were classified as malignant, benign or equivocal. Radiological studies and available clinical information were also used during reading of scans. Review of clinical information, radiological studies and/or follow-up bone scans were used as gold standard. The results of the SPECT and SPECT/CT were compared in terms of proportion of equivocal findings and accuracy. Results: Forty-two patients with 189 skeletal lesions were examined. There was a diverse variety of primary tumours, although the majority had breast (n=22) or prostate cancer (n=8). Overall, SPECT/CT resulted in a significant reduction in the proportion of equivocal findings on both a patient-wise (p=0.0015) and lesion-wise basis (p<0.0001). The overall accuracy of SPECT/CT was significantly higher than that of SPECT on both a patient-wise (p=0.0026) and lesion-wise basis (p<0.0001). Generally SPECT/CT decreased the proportion of equivocal findings and increased the accuracy independent of the presence of bone pain, type of primary tumour, or skeletal region involved. SPECT/CT did not significantly improve the diagnostic confidence of readers in equivocal lumbar lesions although accuracy was significantly improved in this region. Conclusion: SPECT/CT performs significantly better than SPECT alone for the interpretation of equivocal planar lesions. There is no evidence that the benefit of SPECT/CT is dependent on the type of primary tumour or the presence of bone pain. Where resources are limited, SPECT/CT is indicated only in those patients in whom correct classification of the lesions in question is expected to alter the patient’s management. SPECT/CT images should be interpreted with the aid of a diagnostic radiologist or nuclear medicine physicians should acquire sufficient experience in Computed Tomographic image interpretation in order to optimise diagnostic benefit from SPECT/CT.
- ItemThe application of a deep convolution neural network for the automated delineation of the target and organs at risk in High Dose Rate Cervical Brachytherapy(Stellenbosch : Stellenbosch University, 2022-12) Duprez, Didier Raphael Roger; Trauernicht, Christoph Jan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Medical Physics.ENGLISH SUMMARY: Low/middle income countries suffer from large deficits in experienced Radiation Oncologists, Medical Physicists and Radiation Therapists. Due to these deficits, the bottlenecks experienced in the High-dose rate (HDR) cervical brachytherapy treatment planning workflow are amplified. Image-guided HDR cervical brachytherapy is a complex, labour intensive, manual, time-consuming and expertise driven process. Automation in radiotherapy treatment planning, especially in brachytherapy, has the potential to substantially reduce the overall planning time however most of these algorithms require high level of expertise to develop. The aim of this study is to implement the out of the box self-configuring deep neural network package, known as No New U-Net (nnU-Net), for the task of automatically delineating the organs at risk (OARs) and high-risk clinical target volume (HR CTV) for HDR cervical brachytherapy. The computed tomography (CT) scans of 100 previously treated patients were used to train and test three different nnU-Net configurations (2D, 3DFR and 3DCasc). The performance of the models was evaluated by calculating the Sørensen-Dice similarity coefficient, Hausdorff distance (HD), 95th percentile Hausdorff distance, mean surface distance (MSD) and precision score for 20 test patients. The dosimetric accuracy between the manual and predicted contours was assessed by looking at the various dose volume histogram (DVH) parameters and volume differences. Three different radiation oncologists (ROs) scored the predicted bladder, rectum and HR CTV contours generated by the best performing model. The manual contouring, prediction and editing times were recorded. The mean DSC, HD, HD95, MSD and precision scores for our best performing model (3DFR) were 0.92/7.5 mm/3.0 mm/ 0.8 mm/0.91 for the bladder, 0.84/13.8 mm/5.2 mm/1.4 mm/0.84 for the rectum and 0.81/8.5 mm/6.0 mm/2.2 mm/0.80 for the HR CTV. Mean dose differences (D2cc/90%) and volume differences were 0.08 Gy/1.3 cm3 for the bladder, 0.02 Gy/0.7 cm3 for the rectum and 0.33 Gy/1.5 cm3 for the HR CTV. On average, 65 % of the generated contours were clinically acceptable, 33 % requiring minor edits, 2 % required major edits and no contours were rejected. Average manual contouring time was 14.0 minutes, while the average prediction and editing times were 1.6 and 2.1 minutes respectively. Our best performing model (3DFR) provided fast accurate auto generated OARs and HR CTV contours with a large clinical acceptance rate. Future work should focus on including larger datasets to eliminate inconsistencies, as well as focus on automating the generation of treatment plans.
- ItemApplication of gradient dose segmented analysis as a treatment quality indicator for patients undergoing volumetric modulated arc radiotherapy(Stellenbosch : Stellenbosch University, 2022-12) van Reenen, Christoffel Jacobus; Trauernicht, Christoph Jan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Medical Physics.ENGLISH SUMMARY: The gamma analysis metric is a commonly used metric for volumetric modulated arc radiotherapy (VMAT) plan evaluation. The major drawback of this metric is the lack of correlation between gamma passing rates and dose-volume histogram (DVH) values for planning target volumes (PTV). The novel gradient dose segmented analysis (GDSA) metric was developed by Steers et al. to quantify changes in the PTV mean dose (Dmean) for patients undergoing VMAT. In this study, the GDSA metric was applied to 115 head-and-neck cancer patients treated on the Varian Halcyon v2.0 linear accelerator between August 2019 and July 2020 in the Division of Radiation Oncology. The GDSA indicated that a total of 13 patients had received at least one treatment fraction where the PTV Dmean exceeded 3% compared to the first treatment fraction. The kilovoltage cone-beam computed tomography (kV CBCT) images of these patients were analysed to determine the cause. The maximum predicted change in the PTV Dmean was 4.83%. Measurable changes in anterior-posterior and lateral separations were observed for 8 out the 13 patients (62%) where the change in PTV Dmean exceeded 3%. The maximum calculated effective separation change diameter was calculated as 3.86 cm. In cases where the change in PTV Dmean was less than 3%, no measurable separation changes were observed. The pitch-, roll- and yaw-rotational errors were quantified as the Halcyon treatment couch does not allow for online rotational corrections. The maximum pitch, roll and yaw rotational errors were 3.91º ± 0.89º, 3.07º ± 0.51º and 2.62º ± 0.40º, respectively. The mean errors were 0.9º, 0.45º, and 0.43º, for pitch, roll and yaw, respectively. The obtained results demonstrated that large deviations in PTV Dmean (>3%) were more likely due to change in effective diameter, whereas small deviations in PTV Dmean combined with separation changes less than 1 cm, were more likely caused by errors in pitch for long treatment fields. Weight loss during radiotherapy is well documented and proven to be the highest among head-and-neck cancer patients. The GDSA easily be implemented to identify setup/immobilization errors, as well as aid the department in scheduling new CT scans for patients experiencing continuous weight loss before significant differences in dose delivery occur.
- ItemBrain SPECT in patients with neuropsychiatric SLE : the additional value of semi-quantitative analysis(Stellenbosch : University Stellenbosch, 2009-12) Khider, Mohamed Abdelrahman; Warwick, James; Whitelaw, Dave; University of Stellenbosch. Faculty of Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH ABSTRACT: Introduction: There is conflicting data on the value of single photon emission tomography (SPECT) for the diagnosis of neuropsychiatric SLE (NPSLE). Visual assessment of brain SPECT scans is the standard approach in clinical practice. However the definition and identification of significant changes may be limited by a high interobserver variability, especially in centres with limited experience. This may be reduced by a more objective semi-quantitative assessment. The objectives of this study were to determine the sensitivity and specificity of SPECT for the detection of NPSLE at our institution using visual assesment, to determine the additional value of using an objective semi-quantitative diagnostic criterion, and to investigate the correlation between abnormal perfusion pattern and clinical NPSLE classification in patients with active NPSLE. Material and methods: Nineteen patients with NPSLE and 19 normal controls were studied with brain SPECT. Scans were interpreted blindly by two nuclear medicine physicians using two methods; visual and semi-quantitative assessments. In the visual method, overall visual impression was recorded for each scan using a four point scale, where A=normal, B=probably normal, C=probably abnormal, and D=abnormal. In addition, each brain region was assigned a severity score from 0=normal perfusion to 3=severe hypoperfusion. In the semi-quantitative assessment, ten-band color scale was used, and perfusion deficit was quantified on the side with the lower color intensity comparing to the contralateral side. A score was given to the region with perfusion deficit according to the difference (in color bands) between the two hemispheres. Analysis was performed for the visual assessment method (overall impression and severity scores) and the semi-quantitative assessment method using a receiver operator characteristic (ROC) curve. Optimal cut-off points were determined and the accuracy of the different techniques was also compared statistically. Finally, the correlation was determined between the SPECT perfusion pattern and the clinical pattern of disease. Results: An ROC curve analysis for the overall visual impression resulted in an area under the curve of 0.76. At a cut-off point of C (probably abnormal), brain SPECT had 89% sensitivity and 57% specificity for the diagnosis of NPSLE. The severity score which include the total severity score and the modified total severity score resulted in areas under the curve of 0.75 and 0.79 respectively. The semi-quantitative assessment resulted in areas under the ROC curve of 0.80. Statistically, there was no difference between the overall visual impression, visual severity scores, and the semi-quantitative assessment. Agreement analysis between the SPECT pattern and clinical pattern of disease showed agreement in 91.6% in the diffuse pattern, whereas agreement in the focal pattern was seen in only 42.8%. Discussion and Conclusion: In this study, we found that brain SPECT is able to diagnose active NPSLE with a high sensitivity and moderate specificity. The overall visual impression, visual severity scores, and the semi-quantitative assessment showed no significant differences between the techniques. The use of the semi-quantitative assessment described may be useful in centers with limited experience in the interpretation of brain SPECT. The correlation between the SPECT pattern and clinical disease pattern may provide some insights into the pathophysiology of NPSLE.
- ItemBreast cancer diagnosed in women with the Human Immune-Deficiency Virus (HIV)(Stellenbosch : Stellenbosch University, 2014-12) Langenhoven, Lizanne; Barnardt, Pieter; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.ENGLISH ABSTRACT: Background: HIV is the defining pandemic of our era, with an estimated 5.9 million people infected in South Africa according to World Health Organization (WHO) estimates for 2011. The expression and treatment of non-AIDS defining cancers has become an important consideration in this cohort, as antiretroviral therapy (ART) has prolonged survival in a subgroup previously at risk of early mortality. Study Design: A retrospective cohort study of all women seen at the Combined Breast Cancer Clinic at Tygerberg Hospital between January 2010 and December 2011, stratified into three subgroups based on HIV status. Methods: Of the 816 patients screened, 586 met inclusion criteria; of which 31 (5.3%) patients were HIV positive, 420 (71.7%) HIV negative, and 135 (23%) had an unknown HIV status. The disease phenotype was described in each subgroup, as well as toxicities associated with standard chemotherapy regimens, with an emphasis on completion rates of systemic cytotoxic treatment. The insult of cytotoxic therapy to the CD4 count was described for this cohort. Results: Women with HIV had a statistically significant (p<0.001) younger age at presentation of breast cancer with a median age of 42 years (range 39 – 45 years) in comparison with the HIV-negative cohort with a median age of 54 years (range 53 – 55 years) . No difference was detected in disease phenotype when stage at presentation (p=0.7874), histological subtype (p=0.3375), grade of differentiation (p=0.8297), nodal involvement (p=0.0998) or hormone-receptor positivity (p=0.6285) was considered. Completion rates for systemic chemotherapy were excellent (>90%) regardless of HIV-status and no statistically significant toxicity was observed. The median CD4 count at diagnosis was 477 cells/μL (range 234 – 807 cells/μL), with a nadir value of 333 cells/μL (range 62 – 713 cells/μL), representing a decrease of 30.2% during treatment. One case of suspected treatment-related mortality was recorded. Conclusion: This retrospective study confirmed that women infected with HIV had a younger age at breast cancer diagnosis when compared to women with a negative HIV-status. No difference in disease phenotype could be demonstrated for women with HIV, denoting the coexistence of two common chronic diseases. Chemotherapy was tolerated well, but caused a median decline in CD4-count of 30% during treatment.
- ItemCell biological responses of prostatic tumour cell lines to irradiation and anticancer drugs(Stellenbosch : Stellenbosch University, 2003-12) Serafin, Antonio Mendes; Bohm, E. L. J. F.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Radiation Oncology.ENGLISH ABSTRACT: The "classic" prostate cell lines, DU145, PC-3 and LNCaP, have served as a valuable cell biological model for research into prostate cancer. However, their relevance may be limited because they derive from metastatic, and not from primary normal and tumour epithelium. The cell lines (1532T, 1535T, 1542T, 1542N and BPH-l) have been derived from primary benign and malignant human tumour prostate epithelium and may be more representative. Using these cell lines I have examined the role of basic cell damage responses (repair, checkpoint activation, apoptosis and associated signalling proteins, and the influence of androgen status) in cell inactivation, and its relevance to treatment. Numerous studies have suggested that loss of p53 function leads to resistance to chemotherapeutic agents and irradiation. It is shown here that the p53-inactive cell lines are, in fact, the most sensitive to chemotherapeutic agents such as etoposide, vinblastine and estramustine, whilst the p53 wild-type cell line, LNCaP, is the most radiosensitive. Notwithstanding the effects of p53 degradation by the HPV -16 E6 viral protein, the results on chemosensitivity raises the possibility that different chemotherapeutic agents may have different p53-dependent effects in different tumour cells. Androgen deprivation is demonstrated to sensitise prostate cancer cells to chemotherapeutic agents and it is shown that the hormone independent cell lines are the most chemosensitive. The LNCaP cell line displayed an increased resistance to apoptosis induced by etoposide and gamma irradiation, suggesting that androgens are capable of protection against both these DNA damaging agents. The major factors determining radiosensitivity in human tumour cell lines are known to be DNA double-strand break (dsb) induction and repair. In the prostate cell lines I find that cellular radiosensitivity correlates with the number of DNA double-strand breaks measured within 2 hours of irradiation, and that the more radioresistant cell lines show better repair competence. Conclusions as to the influence of androgen dependence on radiosensitivity and repair are not possible at this stage since only the LNCaP cell line was androgen sensitive. The fact that the 2 hour repair period can separate radiosensitive from radioresistant cells in 2 groups of human tumour cell lines highlights the role of non-homologous end-joining repair. This has implications for therapy, and is consistent with the clinical observation that prostate tumours can be successfully controlled by low dose rate-brachytherapy. To evaluate the role of apoptosis, cells were exposed to TD50 concentrations of chemotherapeutic drugs, and 60Co y-irradiation. Apoptosis was found to be low, overall, and ranged from 0.1% - 12.1%,3.0% - 6.0% and 0.1% - 8.5% for etoposide, estramustine and vinblastine, respectively. The percentage of cells undergoing druginduced apoptosis was, on average, higher in the tumour cell lines than in the normal cell lines. Gamma irradiation-induced apoptosis levels ranged from 1.3% - 7%. The LNCaP cell line yielded the lowest percentage of apoptotic cells after exposure. The l532T cell line yielded the highest percentage of apoptotic cells after exposure. Apoptotic propensity did not rank the cell lines according to their radiosensitivity. Immunoblotting demonstrated that the apoptosis-associated proteins, bax and bcl-2, are expressed at a basal level in all the cell lines tested, but no increase was detected after exposure to TD50 doses of etoposide, vinblastine and estramustine. The ratio of bax and bcl-2 also was not altered by DNA damage. No evidence was found that a correlation may exist between reproductive cell death and the expression of genes which control apoptosis. My results show that apoptosis is not a major mechanism of drug- or radiation-induced cell death in prostate cell lines. In conclusion, loss of p53 function and loss of androgen dependence was not found to be correlated with resistance of tumours to chemotherapeutic drugs. Cellular radiosensitivity was found to be correlated with the number of DNA double-strand breaks remaining after 2 hours of repair. The more radioresistant cell lines showed better repair competence. Apoptosis and genes affecting apoptosis, such as p53 and members of the bcl-2 family, do not seem to contribute significantly to the sensitivity of prostate cancer cells to anticancer drugs and irradiation.
- ItemDescriptive epidemiological study of head and neck cancers at a single institution in Southern Africa(Stellenbosch : Stellenbosch University, 2019-12) Naidoo, Komeela; Simonds, Hannah M.; Afrogheh, A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.ENGLISH SUMMARY : Head and Neck Cancers (HNCs) constitute a major public health concern worldwide. The incidence is approximately two times more in less-developed regions as compared to more developed regions. The estimated incidence in sub-Saharan Africa is 27593 per 100000 with a cumulative risk of 0.66. We evaluated patient demographics, risk factors, tumours characteristics, prognostic factors, disease stage, treatment intent and treatment modality in a cohort of patients with HNC in Cape Town, SA. Records of all HNC patients that presented to Tygerberg Hospital oncology department between 1 January 2015 and 31 December 2017 were reviewed. The following variables were described: patient demographics, which include age, sex, HIV status, and socio-economic status as well as tumour characteristics, risk factors, treatment intent and treatment modalities. Data was collected from 854 patients seen between 2015 and 2017. There were 603 (71%) male and 251 (29%) female. The male to female ratio was 2.4:1. The age range was 10-89 years (median age 58 years). Smoking was a risk factor in 737 (86.3%) and alcohol in 634 (74.2%) of patients. Of the 167 patients with oropharyngeal primaries, 16 (9.58%) patients had p16 positive, 78 (46.70%) were p16 negative and the p16 status was unknown in 73 (43.7%). The most common site was the oral cavity (n=320) and the most common sub-site was the anterior tongue (n=137). Eleven patients had two separate primaries at the time of diagnosis. In total, 466 patients (53.87%) presented with locally advanced, stage IVA disease. The median age of diagnosis, the most predominate primary site; histological subtype and stage at presentation were consistent with that reported in the literature. We have demonstrated that the majority of patients present at a late stage, with locally advanced disease. This together with the predominate risk factors of smoking and alcohol consumption is a potential target for health campaigns and awareness programmes. This cohort will be followed up for treatment outcomes and survival rates.
- ItemDesign of a universal phatom for quality assurance in diagnostic radiology x-ray imaging(Stellenbosch : Stellenbosch University, 2017-12) Annemari, Groenewald; Groenewald, Wilhelm Adolf; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiodiagnosis.ENGLISH SUMMARY : Introduction: In medical X-ray imaging several diagnostic x-ray imaging modalities are applied to enable disease diagnosis, i.e. general projection radiography, fluoroscopy, mammography and Computed Tomography (CT) scanning. X-ray images must be of sufficient quality to enable accurate diagnosis. Image quality is quantified using suitable phantoms to ensure that equipment failure is detected before patient care is affected. A variety of phantoms are commercially available. However, these are modality specific, expensive and often complicated to use. In resource limited institutions, like many in Africa including South Africa, three problems are identified in the field of diagnostic radiology X-ray image quality control (QC). These are cost, man power and expertise and time constraints. A gap thus exists in the market for a single universal image quality assurance (QA) phantom, capable of doing all required QC tests for all X-ray imaging modalities. A phantom, answering to this requirement, in addition must be user-friendly and cost- and time-efficient. Aim: To design, develop, manufacture, test and validate a universal image QA phantom for diagnostic radiology X-ray imaging. The phantom must be compact, unique, universal (i.e. not modality specific), easy and quick to use and manufactured at a substantially reduced cost compared to the commercially available options. Materials and methods: Using literature studies on existing commercial phantoms for guidance, a prototype universal phantom was designed, manufactured and tested for all X-ray imaging modalities. From the prototype results, adjustments were made and the universal image quality phantom was developed and manufactured. The phantom is made from high density polyethylene and houses several inserts of different materials to assess sensitometry, image uniformity, limiting resolution, image noise, i.e. signal-to-noise (SNR) and contrast-to-noise (CNR) ratios, geometry and measurement tools, standard signal, low contrast detectability, positioning and alignment, artefacts and visual image quality inspection. For CT scanning the phantom measures slice thickness and for mammography masses, fibres and micro-calcifications are evaluated. Data analysis software was developed for analysis of obtained images and a complete step-by-step user’s manual was prepared. Reproducibility testing was performed on the phantom, using Department of Health (DoH) specified limits. Independent validation of the phantom package (i.e. phantom, software and manual) was done by three independent medical physicists. They compared the phantom to the commercial phantoms in general use in their institutes. Results: The universal image QA phantom and accompanying data analysis software produced reproducible results for all imaging modalities, within the accepted DoH tolerance levels. The independent validation results proofed that the phantom package was easy to transport, light weight and compact, easy to set-up and use, versatile, cost effective and user friendly. Discussion and conclusion: From the reproducibility testing and independent validation results it may be concluded that the universal image QA phantom, with accompanying data analysis software and user’s manual, offers an acceptable single phantom solution for medical X-ray imaging. The universal phantom is a cost and time saver and as such could fill a gap in the existing market. In addition, the phantom could also be used by radiographers in resource limited institutions.
- ItemThe effect of reconstruction algorithms (iterative versus filtered backprojection) on the diagnosis of single pulmonary nodules using Thallium-201 and Technetium-99m MIBI SPECT(Stellenbosch : Stellenbosch University, 2004-04) Ambayi, Rudo; Ghoorun, S.; Dupont, P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH ABSTRACT: This study involved 33 patients, 19 men and 14 women. The age range was wide (20-90 years) and median age was 57 years. These patients had a single pulmonary nodule (SPN) defined radiologically as a well defined, round or oval intrapulmonary lung lesion not associated with atelectasis or adenopathy on chest radiography or computed tomography. Patients were investigated with Tc-99m MIBI and TI-201 (25 patients) and with Tc-99m MIBI alone (8 patients). Single photon emission computed tomography images were reconstructed using both iterative reconstruction (Ordered Subsets - Expectation Maximisation: aSEM) and filtered backprojection (FBP), on the Hermes system. Transverse, coronal and sagittal slices were displayed on the screen using a grey scale. The aSEM and FBP images for each study were co-registered semi-automatically using the multimodality programme on the Hermes. The best slice for the lesion was chosen according to the best view used to locate the SPN on chest radiograph. Regions of interest (Ral) were drawn manually outside the outer margin of the detected lesion, first on the aSEM image. This was automatically mirrored on the co-registered FBP image. For most patients, the background was automatically mirrored horizontally on the contralateral side, again, first on the OSEM then automatically on the FBP image. Automatic vertical mirroring or manual horizontal mirroring was used when background was found to be in a visually 'hot' area like the heart or vertebrae. The average counts and standard deviation of the Ral and background were generated automatically. Semi-quantitative image analysis was done by calculating the signal-to-noise ratio (SNR) and tumour-to-background (TIB) ratio using the following formulae: SNR = Mean counts ROI(lesion) - Mean counts background Standard deviation background TIB rati.o = -M---e-a-n-'--c-o--u-n-'t-s- ROI(lesion) Mean counts background Detection was found to be the same for the two reconstruction algorithms, that is, every lesion detected by using OSEM could also be detected by using FBP. However lesion detection did differ between Tl-201 and Tc-99m-MIBI. Sensitivity and specificity were calculated for different thresholds of SNR and TIB ratios. Receiver operating characteristics (ROC) curves were drawn to represent the different sensitivities and specificities at each threshold. Tuberculosis (TB) was not included in this analysis as uptake of Tl-20l was found to be significantly high and comparable to that of malignant nodules. However the effect of OSEM and FBP on the 'positive' TB nodules was assessed separately. By calculating the area under the ROC curves, TI-201 using OSEM was shown to be more accurate at differentiating malignant nodules from benign ones than FBP. Although this difference was not statistically significant (p=0.1 0), there was a clear tendency. The two reconstruction algorithms were found to be almost equally accurate, when using Tc-99m-MIBI, the difference between them being considerably insignificant. In conclusion, it was shown that there is a tendency that OSEM outperforms FBP for studies using Tl-201 but not for Tc-99m-MIBI.
- ItemEvaluation of BCL-2 and PARP-1 as potential therapeutic targets to radiosensitise lung cancer(Stellenbosch : Stellenbosch University, 2021-12) Guillaume, Muteba Mpolesha; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY : Lung cancer remains the most incident malignancy worldwide, representing 13% of all cancers. It is also the leading cause of death in the world, accounting for 18 18.2% of global cancer-related deaths. The burden of lung cancer in Africa is increasing due to ag ageing an and population growth, increased prevalence of risks factors such as smoking, occupational exposure, infections, lifestyle changes, and environmental pollutants. The efficacy of many therapeutic strategies has been hindered by normal tissue toxicity and treatment resistance. For many cancer patients, radiotherapy has been the chosen therapeutic option to minimise cancer cell spread by shrinking the tumour while ensuring protection of normal tissue. There is evidence that small molecule inhibitor s can effectively target cell survival signa signalling pathways, but cancer cell cells manage to find molecular escape routes to either repair the damage or evade cell death. Combination therapy appears to be an appropriate approach to address these challenges. Therefore, targeting more than one component of the cell survival signa signalling pathways could potentially sensitise cancer cells to irradiation and improve the outcome of radiotherapy. The purpose of this study was to evaluate the role of targeting the anti-apoptotic (B-cell lymphoma 2 (Bcl -2)) pathway and the DNA repair (poly (ADP ADP-ribose) polymerase 1 (PARPPARP-1)) pathway with specific inhibitors in modulating the radiosensitivity of a lung cancer cell line ( and an apparently normal lung cell line ( For this, Bcl -2 and PARP PARP-1 were inhibited using ABT ABT-737 and ABT ABT-888, respectively. At a dose of 2 Gy, the typical fractional dose in conventional radiotherapy, combined inhibition of Bcl-2 and PARP-1 or inhibition of Bcl-2 alone resulted in significant radio-sensitisation in only the A549 cells. However, at a larger radiation dose of 6 Gy (a potentially useful fractional dose in hypo-fractionated radiotherapy), inhibition of Bcl-2 and PARP-1 markedly radio-sensitised the apparently normal (L132) and malignant (A549) cell lines, respectively. These findings suggest that use of Bcl-2 and PARP-1 inhibitors might be beneficial when combined with conventional radiotherapy, but not with hypo-fractionated radiotherapy when large fractional radiation doses are employed. However, validation of these results with a larger panel of cell lines is warranted.
- ItemEvaluation of small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 for their radiomodulatory effects in human breast cancer cell lines(Stellenbosch : Stellenbosch University, 2016-12) Hamunyela, Roswita Hambeleleni; Akudugu, John M.; Serafin, Antonio Mendes; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY : Breast cancer remains the most commonly diagnosed cancer in women. It is responsible for 32% of all cancers and 15% of all cancer-related deaths in females. Patients with triple-negative breast cancers (TNBC) constitute about one-fifth of all breast cancer patients. TNBC is an aggressive and heterogeneous disease entity in comparison with other types of breast cancer and, therefore, tends to be resistant to existing treatment regimens, such as, targeted and hormone therapies. Although cancer treatment has evolved from being invasive and highly toxic to being more specific with reduced normal tissue toxicity, intrinsic tumor resistance still limits the benefit of therapy with radiation, drugs, and antibodies. To address this important clinical challenge, attempts have been made to better understand the molecular determinants of treatment resistance. This resistance can be attributed to the heterogeneity in the distribution of potential target antigens in a given tumor cell population, which leads to the inability to effectively target all cells with toxic levels of a particular therapeutic agent. There is evidence to suggest that proliferative pathways of triple-negative tumors are still poorly understood, which could be the reason for the observed treatment resistance. Targeted treatment modalities that are singly effective for triple-negative breast cancer are lacking, partly due to paucity of relevant targets as they are devoid of the human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and oestrogen receptor (ER). Novel treatment approaches are, therefore, needed to overcome the challenges in the treatment of triple-negative breast cancers if treatment outcomes are to be improved. Concomitant targeting of cell signaling entities other than HER2, PR and ER may sensitize triple-negative tumors to radiotherapy. In this study, inhibition of HER2, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and the pro-survival gene (Bcl-2) with small molecule inhibitors, TAK-165 (against HER2), NVP-BEZ235 (against PI3K and mTOR), and ABT-263 (against Bcl-2), singly or as cocktails, resulted in significant radio sensitization of human breast cell lines with features similar to those of triple negative cancers. This radio sensitization was seen at 2 and 6 Gy, indicating that a therapeutic benefit could be derived in conventional as well as stereotactic radiotherapy. A moderate to strong synergism was also demonstrated for NVPBEZ235/TAK-165 and NVP-BEZ235/ABT-263 cocktails. The strongest synergy was seen in the latter cocktail. In conclusion, inhibition of PI3K, mTOR and Bcl-2 could potentially be effective in the treatment of triple-negative breast cancer. The therapeutic benefit can be improved, if the target inhibition is followed by radiotherapy.
- ItemEvaluation of the effect of low and intermediate frequency electromagnetic waves on radiosensitivity(Stellenbosch : Stellenbosch University, 2016-12) Chinhengo, Angela; Akudugu, John M.; Serafin, Antonio M.; Stellenbosch University. Faculty of Medicine and Health Science. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY : The incidence of epidemic Kaposi’s sarcoma in HIV/AIDS patients is high due to their compromised immune system. HIV-positive individuals presenting with cancer tend to be more sensitive to ionizing radiation and are at a higher risk of developing severe side effects during radiotherapy, and there is a need to develop non-invasive methods to preferentially sensitize cancer cells and reduce therapeutic doses. Here, the effects of 100 and 1000 Hz electromagnetic fields (EMF) broadcast via an argon plasma ray tube at 50 W on the radio sensitivity of apparently normal Chinese hamster lung fibroblasts (V79) and human malignant melanoma cells (MeWo) were evaluated using the colony forming assay. Pre-exposure of the fibroblasts to both fields had no effect on their radio sensitivity, if X-ray irradiation followed within 2 h or at 6 h. Significant radio sensitization was observed when X-rays were administered 4 h after EMF exposure. For the MeWo cells, pre-exposure to 100 Hz resulted in a significant radioprotection when irradiation followed within 6 h. However, treatment of these cells with a 1000 Hz field significantly potentiated the effect of X-rays. When cells were irradiated prior to EMF exposure, the V79 cells were marginally protected by the 100 Hz field and sensitized by the 1000 Hz field. In contrast, the melanoma cells were slightly protected by the 1000 Hz field and sensitized by the 100 Hz field. The survival rate of the normal fibroblasts when treated with 2 Gy, in two fractions of 1 Gy 6 h apart, was similar to those obtained when cells received an acute dose of 2 Gy 6 h prior to or after exposure to both EMF frequencies. On the other hand, the melanoma cells were significantly sensitized when they were either treated with a combination of X-rays and then 100 Hz EMF 6 h later or with a combination of either of the EMF frequencies and then X-rays 6 h later. These data suggest that use of electromagnetic fields may sensitize tumours to radiation therapy and reduce normal tissue toxicity. Informed and well-designed combinations of low-medium frequency electromagnetic fields and radiation therapy might be beneficial in the management of cancers, especially epidemic Kaposi’s sarcoma.
- ItemEvaluation of the effect of radiofrequency electromagnetic waves on radiosensitivity(Stellenbosch : Stellenbosch University, 2019-12) Chinhengo, Angela; Akudugu, J. M.; Serafin, A. M.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiobiology.ENGLISH SUMMARY : Cancer is a major cause of human death worldwide, and one of the very real challenges is how to control treatment resistance. An additional challenge is the co-morbidity of cancer, with certain infections complicating its management. Radiotherapy (RT) is considered the first line of treatment for most superficial cancers, as these malignancies tend to respond well to radiation. The use of hypofractionated treatment may be beneficial for certain tumours, but hypofractionation may result in severe side-effects from normal tissue toxicity from which the patient may not recover. To circumvent this, radiation modifying agents that potentiate the tumour inactivating effects of ionising radiation and thereby lead to a reduction in radiation dose and prevent normal tissue toxicity, can be utilised. Magnetic fields have long been suggested as potential enhancers of radiation effects. Studies on the combined biological effects of radiofrequency fields (RFF) and ionising radiation are virtually non-existent. The use of RFF adjuvant to radiotherapy may be beneficial, as they have been shown to exhibit in vitro radiosensitising and radioprotective effects in malignant and normal cells, respectively, with the possibility of a significant dose reduction. There is, however, a need to understand the mechanisms by which these RFF influence radiosensitivity so that they can be employed efficiently as radiotherapy modulators. The main goal of radiotherapy is to kill tumour cells and spare normal tissue, and a good modifying agent would be one that sensitises the tumour whilst protecting normal tissue. This study assessed the effect of radiofrequency fields (RFF), modulated at 100, 1000, 2000 and 4000 Hz, on the radiosensitivity of four cell lines: a p53 mutant melanoma cell line, MeWo; a p53 wild-type melanoma cell line, Be11; a p53 mutant prostate cancer cell line, DU145; and a p53 wild-type normal lung fibroblast cell line, L132. The radiomodulatory effect of radiofrequency fields was evaluated using the colony assay. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD) and micronucleus assays were used to assess the possible mechanisms by which radiofrequency fields influence the radiosensitivity of cells. The data demonstrate that radiofrequency fields are more efficient in modulating large fractional doses of X-rays and could find application in hypofractionated radiotherapy as adjuvants, especially for tumours with low alpha/beta ratios. This can have a positive impact on the management of patients with superficial tumours that may be resistant to low fractional doses of radiation. Radiofrequency fields modulate cellular radiosensitivity in a frequency- and cell type-dependent manner and their effects appear to be linked to p53 status. Cellular responses such as metabolism, DNA damage processing (based on micronuclei formation), and abnormal proliferation (based on binucleation) seem to be underlying factors mediating the radiomodulatory effects of radiofrequency fields. Mechanisms by which radiofrequency fields can possibly modulate radiosensitivity are: amplification of radiation-induced genotoxicity, cell cycle arrest, and disturbance of other cellular biochemical processes that lead to alteration of homeostasis. Alternative ways by which RFF affect radiosensitivity are: interfering with the synthesis and function of charged proteins in the cell leading to programmed cell death or premature cell ageing, perturbation of intracellular calcium ions which can trigger apoptotic or necrotic cell death, and/or modulating the expression of Bcl-2 family proteins. Given this complexity, a potential use of radiofrequency fields as a non-invasive therapeutic modality would require standardisation to establish reproducibility. A more detailed understanding of how radiofrequency fields interact with ionising radiation would also prove beneficial in the broader field of radiation protection.
- ItemExamination of irradiated neuroblastoma and neuroepithelial cell lines for the interrelationship between cell survival, micronucleation, apoptosis and DNA repair(Stellenbosch : Stellenbosch University, 2000-12) Akudugu, John Mbabuni; Bohm, E. L. J. F.; Slabbert, J. P.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Radiation Oncology.ENGLISH ABSTRACT: Predictive assays are of key importance in clinical radiotherapy, chemotherapy and toxicology. Prior to exposing malignant tissues to irradiation or drugs in the clinic, a good understanding of the damage response to the cytotoxic agent is required. Such information is necessary for effective planning and treatment. Regrettably however the methods which detect DNA damage, namely micronucleus, apoptosis and DNA repair assays do not rank cells according to their intrinsic survival response to cytotoxic agents. The application of predictive assays based on micronuclei and apoptosis in the clinic therefore remains unreliable. Using a panel of 7 neuroblastoma and 6 neuroepithelial cell lines, it is shown that damage assays also do not rank cell lines according to cell survival. However, radiosensitivity can be reconstructed from micronuclei formation and apoptosis, and a new parameter, cell death due to small deletions, chromosome aberrations and misrepair. The interrelationships between radiation-induced micronuclei, apoptosis and repair is complex and varies between cell lines. Micronuclei formation and apoptosis are exponentially interrelated. This suggests that these cell inactivation pathways are strongly correlated. Evidence exists to show that the expression of apoptosis and micronuclei is influenced by the extent of DNA double-strand break repair within the first 2 hours after irradiation. Cell lines which repair more damage in the first 2 hours express more micronuclei and less apoptosis. Micronuclei formation and apoptosis and are not significantly correlated with the 20 hours slow repair component. There is however a strong correlation between 20 hours of repair and radiosensitivity, with the more radioresistant cell lines being more repair proficient. This suggests that the 2 hours (fast) DNA repair component is more error prone, and that cells lines repairing more damage late after irradiation tend to show better survival. In conclusion, micronuclei formation, apoptosis and DNA repair are strictly cell type specific and are not suitable for predicting radiosensitivity in terms of cell survival. However, these assays are very useful for studies on the influences of dose modifying agents i.e. oxygen tension, radiation modality, pH, cytotoxic sensitisers and radiation protectors which alter cellular responses and provide insight into damage mechanisms.
- ItemExtended Cr-51 RBC combined with Tc-99m RBC for the detection and localisation of occult GIT bleeding(Stellenbosch : Stellenbosch University, 2014-04) Modebe, Emmanuel Obinna; Ellmann, Annare; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology, Nuclear Medicine. Radiodiagnosis.ENGLISH ABSTRACT: Background Occult blood loss from the gastrointestinal tract (GIT), causing iron deficiency often with anaemia, can be diagnostically and therapeutically challenging. This is because the endoscopic and radiologic tests may be negative due to the slow, chronic and intermittent nature of the gastrointestinal bleeding, making timing key in detection and localisation of the bleed. These limitations can be approached using two different radioactive isotopes. Firstly, we tested the sensitivity of extending Cr-51 RBC for 21 days relative to 5 days to detect GIT bleeding and its use to optimise timing of a Tc-99m RBC study for GIT blood loss localisation. Finally, we tested if the information provided by the Tc-99m RBC study aided gastroenterologic intervention for anatomical localisation of a lesion. Method In this retrospective review, after obtaining institutional and ethics committee approval, records of patients referred for evaluation of possible GIT blood loss were reviewed. In each; daily appearance of radiochromium in stool was measured in the whole body counter. In those cases exceeding 50 ml/day, a technetium-99m (Tc-99m) localization study was performed. These studies were correlated with clinical findings. Results A total of 59 Cr-51 RBC studies were carried out in 36 females and 21 males (n = 57). In 32 (54%) the radiochromium results were positive with 75% of the bleeding incidences occurring after 5 days of stool collection. Of 17 cases in whom Tc-99m RBC imaging studies were performed, 14 (82%) were positive with specific anatomical sites successfully defined in twelve. In all patients with blood loss of >100 ml/24h, Tc-99m RBC were positive and localised. Ten of the 17 Tc-99m RBC studies were further investigated and half diagnosed with small-bowel angiodysplasia. Conclusion This sequential twin isotope method is practical in revealing otherwise silent intestinal haemorrhage. Although it has good patient acceptability and clinical as well as diagnostic utility in management, further studies are required to clearly establish a cut-off level of blood loss for performing imaging studies and the impact of the findings on the overall patient management.
- ItemGlomerular filtration rate measurement and estimation : improvement and validation of existing methods(Stellenbosch : Stellenbosch University, 2019-12) Holness, Jennifer Lyn; Warwick, James Mathew; Davids, Mogamat Razeen; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY : Glomerular filtration rate (GFR) is regarded as the best measure of kidney function. It can either be measured or estimated. This dissertation aims to provide a better understanding of GFR measurement in order to improve its performance and interpretation. It also aims to validate GFR estimation in local populations and to demonstrate the utility of simple adaptations of existing equations to improve estimation. On completion of a GFR measurement, various quality control (QC) checks are performed to ensure the accuracy of the result. However, this requires comparison with clearly defined reference ranges. In a study of healthy, potential kidney donors, reference data for two QC parameters were defined. In a study analysing the effect of measurement errors on GFR, the single-sample method was found to be the most robust technique overall, although for all methods measurement error was generally insignificant compared to expected biological variation in GFR. However, at low GFR values measurement errors were shown to affect all methods significantly. Errors in measurement of the doses were found to have the greatest impact on accuracy. Using nuclear medicine techniques 51Cr-ethylenediaminetetra-acetic acid (51Cr-EDTA) is the most commonly used and widely studied exogenous filtration marker. However, 99mTc-diethylenetriaminepenta-acetic acid (99mTc-DTPA) is gaining favour because of a few technical advantages it has over 51Cr-EDTA, its lower cost, and recent issues with the availability of 51Cr-EDTA. In response to a systematic review suggesting that GFR measurement from the plasma clearance of 99mTc-DTPA was inaccurate, a mini meta-analysis was performed that demonstrated excellent agreement between 51Cr-EDTA and 99mTc-DTPA clearance, thus supporting the use of 99mTc-DTPA as a reliable alternative. Where GFR cannot be routinely measured, it is frequently estimated using a creatinine-based equation. The use of any equation first requires validation in the population in which it will be used. In a study evaluating the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in non-cancer, mixed ancestry adults, both equations were found to perform well. However, in a study that evaluated equations in adults with cancer, the GFR estimates were found to be biased and imprecise. This study highlighted the limitations of using estimated GFR for guiding management decisions in cancer patients. A further study evaluated 11 estimating equations in non-cancer and cancer populations of South African children. The accuracy of all estimates was poor, particularly in the cancer group. Given the extensive use of GFR estimates in South Africa, these findings have profound implications for their use in the management of children and adults with cancer in this country. Developing new equations for a specific population requires large datasets and incurs costs that are impractical in most middle- or low-income countries. A simpler alternative is to adapt existing equations. This work demonstrates the application of a relatively simple approach to adapt existing equations, using modest amounts of data and a readily available Microsoft® Excel-based tool. While this approach is simple and likely to require further refinement, its utility was demonstrated in paediatric and adult cancer populations.
- ItemHow efficient is Technitium -99m labelling of erythrocytes in patients with malaria?(2011) Ekoume, F. P.; Rubow, S. M.ENGLISH ABSTRACT: With the expansion of Nuclear Medicine techniques in developing countries, it is essential to ensure a quality imaging procedure. In the case of red cell labelling, any factor which interferes with the labelling can lead to sub-optimal studies. With regard to the high incidence of malaria in sub-Saharan African countries in general and in Cameroon particularly, a high percentage of patients referred to Nuclear Medicine departments also have malaria. The question arose whether the presence of Plasmodium in erythrocytes or anti-malarial medication could affect the labelling of erythrocytes with technetium-99m. The aim of this study was to investigate the impact of Plasmodium and anti-malarial medication on Tc-99m red cell labelling efficiency with in vitro kits in a population with a high prevalence of malaria infection. Approval for this study was obtained from ethics committees of both institutions. Three groups of 30 patients were enrolled in the study after giving informed consent: 1. Smear-negative patients in an area where malaria is endemic (control group M-). 2. Patients with malaria as determined by a positive malaria smear test (group M+). 3. Patients with malaria and on anti- malaria medication (group Mm). From each patient, a 5 ml blood sample was drawn in a heparinised blood collection tube. The red blood cells of each sample were labelled in vitro with Tc-99m, using an in vitro red blood cell kit. Labelling efficiency of the 3 groups was compared. The average labelling efficiency was 98.2% ± 2.3% in malaria-free individuals, 98.6% ± 2.6% in patients with malaria but not on treatment, and 98.6% ± 1.1% in patients with proven malaria on quinine treatment. Non parametric data analysis using the Kruskal-Wallis ANOVA test for the percentage of labelling efficiencies showed a P-value of 0.2117 which was a confirmation that there was no significant difference between the labelling efficiencies for the three groups. Radioactively labelled red blood cells are used in various nuclear medicine studies. Various drug therapies, including antibiotics, are known to either inflict direct or indirect damage to RBCs or their precursors or to impact influx or efflux of Tc-99m-pertechnetate into or out of RBCs, thereby decreasing labelling efficiency to such an extent that poor and inaccurate diagnostic information is obtained. The results of this study indicate that malaria parasites and anti-malarial treatment with quinine do not affect in vitro erythrocyte labelling with Tc-99m, and should thus not interfere with nuclear medicine investigations.
- ItemImaging of renal hyperparathyroidism using SPECT/CT with low-dose localizing CT(Stellenbosch : Stellenbosch University, 2013-12) Doruyter, Alexander Govert George; Warwick, James Matthew; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Division of Nuclear Medicine.ENGLISH ABSTRACT: Background: Hybrid imaging using single photon emission computed tomography/low dose (x-ray) computed tomography (SPECT/LDCT) is of benefit in preoperative scintigraphy of primary hyperparathyroidism. The role of SPECT/LDCT in preoperative assessment of renal hyperparathyroidism has not yet been examined. The aim of the study was to determine whether SPECT/LDCT conferred any benefit over SPECT alone in terms of detection and/or localization of hyperfunctioning parathyroid tissue in this patient group. Methods: A retrospective study of patients with renal hyperparathyroidism and positive planar and SPECT scintigraphy was undertaken. All patients underwent planar scintigraphy using 99mTc-pertechnetate immediately followed by 99mTc-sestamibi as well as SPECT/LDCT 60 min after sestamibi injection and a delayed static image to assess for differential washout at 2-3 hours. Planar subtraction images were generated. For each patient, two nuclear physicians reported on planar+ SPECT images followed by planar + SPECT/LDCT images (assisted by a radiologist). Confidence for the presence of hyperfunctioning parathyroid tissue as well as confidence of location was scored on a Likert-type scale. Interpretation of planar + SPECT was compared with interpretation of planar + SPECT/LDCT. The impact of LDCT on equivocal lesions and number of ectopic lesions detected was also assessed. Results: Twenty patients (M:13; F:7) imaged between February 2008 and June 2011 were included [mean age: 40 years (24 – 55)]. Mean creatinine was 687 μmol/l (169-1213), mean corrected calcium: 2.55 mmol/l (1.95-3.33) and median PTH 167 pmol/l (2.4 - >201). Thirty-five lesions were detected on planar and SPECT and this was unchanged after assessment of the LDCT data. Confidence for the presence of parathyroid pathology changed in 5 patients (5 lesions) with the addition of LDCT. LDCT changed the mean confidence of parathyroid pathology from 3.17 to 3.29 (p=0.16). Addition of LDCT reduced the number of equivocal lesions from 18 (14 patients) to 14 (10 patients) (p=0.13). The addition of LDCT changed localization in 4 lesions (3 patients). Confidence in localization of pathology changed in 9 lesions (7 patients) and the mean localization confidence score was improved from 4.2 to 4.46 (p=0.002) with LDCT. The number of lesions classified as ectopic increased from 5 (on planar+SPECT) to 8 (with addition of LDCT) (p=0.25). Conclusion: In renal hyperparathyroidism SPECT/LDCT altered localization of lesions detected on planar and SPECT alone and improved reader confidence of localization accuracy. SPECT/LDCT conferred no additional benefit over SPECT in terms of detection, confidence of parathyroid pathology or ability to distinguish equivocal from non-equivocal parathyroid lesions. The addition of LDCT did not detect significantly more ectopic lesions. Whereas the minor improvement in reader confidence of localization (with addition of LDCT) was of questionable clinical significance, we speculate that the changed and presumably improved localization of lesions on SPECT/LDCT had potential clinical impact in a significant proportion of patients. On this basis we recommend the use of hybrid SPECT/LDCT in imaging of renal hyperparathyroidism when surgery is considered.
- ItemImplementation of guidelines on hospital radiopharmacy in low-income settings(Stellenbosch : Stellenbosch University, 2020-12) Ekoume, Fany Pricile; Rubow, Sietske Margarete; Boersma, Hendrikus H.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. Nuclear Medicine.ENGLISH SUMMARY : Although radiopharmacy is more than 50 years old, it is still in a stage of rapid development. This dissertation focuses on quality issues in radiopharmacies in developing countries. Guidelines for radiopharmacy practice in many countries prescribe complex facilities, especially air handling units, and extensive quality assurance and documentation requirements. In developing countries, these guidelines are currently not always met. In numerous countries in Africa, enforcement of the international guidelines would lead to closure of radiopharmacies, and consequently, loss of Nuclear Medicine services. The question arises what the consequences of not meeting the requirements of the guidelines are, and if practice can be improved without major expenditure. This study considered certain aspects of Good Radiopharmacy Practice (GRP) recommendations and collected information from both a relatively well-equipped facility at Tygerberg Hospital (TBH) in South Africa, and a more basic radiopharmacy facility at Yaoundé General Hospital in Cameroon (YGH) to investigate the conditions that will ensure safe and effective products. Factors assessed include efficacy and microbial safety of the radiopharmaceuticals, with some comparison to a state-of-the-art Good Manufacturing Practice (GMP) compliant radiopharmacy at the University Medical Centre Groningen (UMCG) in the Netherlands. An adapted version of the Quality Management Audits in Nuclear Medicine (QUANUM) tool, tailored for the radiopharmacy context, was used to determine the status of practice in the two African radiopharmacies. Once the current situation and product quality in these radiopharmacies was determined, basic, low-cost interventions to minimise deficiencies were implemented at YGH and the effects of the interventions were assessed. Where the necessary level of safety and efficacy could not be met with currently available systems despite interventions, this was reported. The efficacy of radiopharmaceuticals depends on their radiochemical purity. As lack of validation of analytical methods was one of the shortcomings noted in the YGH audit, experimentally validating a cost-effective radiochromatography method to be used at YGH was the first step of corrective actions implemented. As the provision of clean air and maintenance of air handling systems and equipment require a large budget, special emphasis was placed in three further chapters of the dissertation on assessment of microbial contamination of products, and measures to ensure sterility of products. At YGH, we reached better control of microbiological air quality. This was achieved by the implementation of simple microbiological air sampling methods, and subsequent introduction of hygienic and procedural improvements. Sterility testing of SPECT radiopharmaceuticals showed a low contamination rate at both TBH and YGH. Nevertheless, preparing radiopharmaceuticals in a well-maintained laminar air flow cabinet is recommended in order to reduce the risk of contamination of products by airborne microorganisms. The serious consequences that could arise from not meeting GRP requirements, include transmission of microbial infection to patients or administering radiochemically impure products. This dissertation presents the first work evaluating an affordable approach of the implementation of GRP in sub-Saharan Africa. It is highly recommended to all radiopharmacies in the developing world to adapt GRP in their context and to implement an optimised quality assurance programme, striving for continuous improvement.
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