Spectral Analysis Using Regularized Non-Negative Least-Squares Estimation

The implementation of spectral analysis techniques involves solving a highly underdetermined linear system equation and is prone to the effect of measurement noise. The authors propose to use a regularized non-negative least-square estimator to stabilize the implementation of the technique. They introduce a penalty term in their formulation of the function to discourage disparities in tracer kinetics between neighboring pixels and use an iterative method to impose positivity constraints. The authors show results from analysis of FDG thorax images of patients suspected to have cancers and summarize their findings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85892/1/Fessler137.pd

Deadtime correction for two multihead Anger cameras in 131I dual‐energy‐window‐acquisition mode

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134914/1/mp8162.pd

Volume reduction versus radiation dose for tumors in previously untreated lymphoma patients who received iodine-131 tositumomab therapy

BACKGROUND A Phase II study of previously untreated patients with malignant low grade follicular lymphoma given a combination of unlabeled tositumomab and tositumomab labeled with iodine-131 has recently been completed. The responses of these patients have been characterized, and for some of them tumor dosimetry during therapy has been estimated not only by pretherapy tracer conjugate views but also by a hybrid method. METHODS Available patients were studied if they had had a pelvic or abdominal tumor evaluation by single photon emission computed tomography (SPECT) and achieved a partial response. A tumor outlined on the iodine-131 conjugate-view images was called a composite tumor. Its volume estimate came from multiple, not necessarily contiguous, regions of interest (ROI) on the pretherapy computed tomography (CT) scan. Its radiation dose was estimated from the weeklong series of pretherapy images and standard Medical Internal Radiation Dose methods. Computed tomography ROI were also grouped into smaller, contiguous volumes that defined individual tumors. Their radiation doses were estimated by the hybrid method. This method employed the activity measured for each individual tumor by a single intratherapy SPECT scan, as well as the tumor's volume, to individually normalize the composite time-activity curve as appropriate. The individual normalization factors then converted the composite radiation dose to radiation doses for individual tumors. Reduction in tumor volume was calculated for both composite and individual tumors at 12 weeks posttherapy. RESULTS For 14 composite tumors in 10 patients, the median pretherapy volume was 170 cm 3 . Application of a sigmoidal curve function to the plot of volume reduction versus radiation absorbed dose resulted in degeneration of the curve into a straight line with a negative slope. There was no statistical significance in the relationship ( P = 0.73). For 43 individual tumors, the median pretherapy tumor volume was 26 cm 3 . The plot of volume reduction versus dose was fairly well fit by a sigmoidal curve, and the relationship approached statistical significance ( P = 0.06). The representation assigned 56% of the shrinkage to the effects of unlabeled tositumomab. For the subset of individual tumors with a pretherapy volume less than 10 cm 3 from 6 patients (n = 15), the relationship was significant ( P = 0.03). The sigmoidal representation assigned only 12% of the shrinkage to unlabeled tositumomab, as contrasted with 72% for tumors with pretherapy volume greater than 10 cm 3 . CONCLUSIONS For patients who attained a partial response, analysis of individual tumors by a hybrid dosimetric method led to a dependence between volume reduction at 12 weeks and radiation dose that tended to be significant. The same was not true with dosimetry of composite tumors based on pretherapy conjugate views alone. It appeared that volume reductions from both unlabeled antibody and radiation dose were important in tositumomab therapy of lymphoma patients, with unlabeled antibody relatively more important for larger tumors. Cancer 2002;94:1258–63. © 2002 American Cancer Society. DOI 10.1002/cncr.10294Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34359/1/10294_ftp.pd

Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131 I-MIBG (4.9–8.1 GBq or 132–220 mCi) and ten were given 125 I-MIBG (8.3-30.0 GBq or 224–809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131 I-MIBG; GBq/kg of body weight; and GBq/m 2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131 I-MIBG, the highest correlation was obtained between cGy and the logo 10 -transformed platelet ratio ( r =−0.86), but comparison of GBq/m2 and the platelet nadir ( r =−0.76) or the platelet ratio ( r =−0.74) or the log 10 − transformed platelet ratio ( r =−0.73) gave comparable and statistically significant results. For treatments with 125 I-MIBG, significant correlations were obtained between GBq/m 2 and the platelet ratio ( r =−0.81) or GBq/kg and the log 10 − -transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131 I-MIBG was 2.6 times more potent than 125 I-MIBG in causing a platelet ratio of 0.1. Thus, in predicting toxicity, therapeutic doses of 131 I-MIBG expressed as GBq/m 2 performed satisfactorily and almost as well as whole-body cGy, and treatment doses of 125 I-MIBG expressed as GBq/m 2 or GBq/kg performed satisfactorily and much better than whole-body cGy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46835/1/259_2004_Article_BF00182305.pd

Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient

The dosimetry for two, similarly sized tumours in a lymphoma patient being treated with non-bone marrow ablative, monoclonal antibody therapy is reported. The 45-year-old man was infused with 2.48 GBq (67 mCi) of 131 I-labelled MB-1. Prior to therapy, a time series of diagnostic conjugate-view images and a radionuclide transmission scan were obtained and processed to obtain time-activity curves. Starting 2 days after the therapeutic infusion of radioactivity, a second conjugate-view time series was obtained. At that time, a quantitative single-photon emission tomography (SPET) acquisition was also carried out. Pre- and post-therapy X-ray computed tomography scans demonstrated a percentage reduction in volume for the right tumour which was 3.8 times that for the left tumour. In contrast, diagnostic conjugate views by themselves estimated the absorbed dose to be the same for the two tumours. Addition of therapy conjugate-view data increased the right-over-left ratio but only to 1.22. Normalizing either time-activity series by the intra-therapy SPET results increased the ratio to greater than 1.5. We assume here that a differential dose is correct according to the differential tumour shirnkage. One can further assume that the largest ratio corresponds most certainly to the most accurate dosimetric method. Other assumptions are possible. While additional study is essential, data from this patient suggest that the preferred dosimetric method is intra-therapy SPET normalization of either time series.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46832/1/259_2005_Article_BF02258433.pd

Testing of local gamma-ray scatter fractions determined by spectral fitting

The spectral-fitting method of correction for gamma-ray Compton scattering within objects separates the unscattered and scattered components of locally measured energy spectra. Here, the authors employ a third-order polynomial for the scattering and an approximately constant fitting window. A scatter fraction, defined as total scattered over total unscattered counts within a 20% window, is calculated for each point in the Anger camera images. These scatter fractions are tested against those from Monte-Carlo simulation for 99mTc and against results from semiconductor detector measurements for 131I. A radioactive sphere at several locations within a non-radioactive cylinder and the inverse are imaged for the testing. For one case, reproducibility of the spectral-fitting scatter fraction as a function of the number of unscattered counts within the 20% acceptance window was also determined.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48957/2/pb910203.pd

Competence to capability: An integrated career framework for sonographers

Introduction Within the United Kingdom sonographers, with ultrasound as their core role, currently have a primary registration as a radiographer or another health professional. Entering with masters level qualifications, and often exhibiting a higher career banding, the sonographer career structure does not align comfortably with the existing health professional frameworks. This study aimed to explore the attitudes and opinions of a sample of practicing sonographers concerning a potential graduate sonographer role and the development of a clinical competence framework required to provide a skills escalator. Methods A qualitative study using an interpretative framework was undertaken using semi-structured interviews. A homogeneous sample population of ten participants was selected using theoretical purposive sampling. The interview transcripts were thematically analyzed and coded. Results The themes of implementing change and clinical frameworks were identified along with a sub-theme of clinical competence boundaries. All participants found it challenging to identify a role or clinical competences that a band 5/graduate sonographer could undertake, though more suggestions were offered for a band 6 sonographer. Conclusion Whilst, within the literature, clinical competences were agreed to provide the cornerstone for defining clinical roles there was some dispute as to the appropriateness of the use of core clinical competences for defining the scope of practice of health professionals above entry level to the profession. The data collected in this study demonstrated that there were skills development between graduate, specialist, advanced and consultant practitioners. Participants were focussed on clinical skills rather than wider capability skills. It is recommended that in order for advanced practice sonographers to map to the new ACP framework less focus on competence and a greater consideration of capabilities is required

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the dopamine D-2 receptor occupancy of olanzapine in rats

A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of olanzapine in rats using the exposure (plasma and brain concentration) and D2RO profile obtained experimentally at various doses (0.01-40 mg/kg) administered by different routes. A two-compartment pharmacokinetic model was used to describe the plasma pharmacokinetic profile. A hybrid physiology- and mechanism-based model was developed to characterize the D-2 receptor binding in the striatum and was fitted sequentially to the data. The parameters were estimated using nonlinear mixed-effects modeling . Plasma, brain concentration profiles and time course of D2RO were well described by the model; validity of the proposed model is supported by good agreement between estimated association and dissociation rate constants and in vitro values from literature. This model includes both receptor binding kinetics and pharmacokinetics as the basis for the prediction of the D2RO in rats. Moreover, this modeling framework can be applied to scale the in vitro and preclinical information to clinical receptor occupancy

Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRgluvaried among different tumor lesions, but mean Vdwas comparable in all lesions. After one course of chemotherapy, mean MRgludecreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vddecreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRgluresponse could be very heterogeneous, even within similar types of metastases. BF and MRgluincreased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRgluchanges separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRgluparameters can be remarkably heterogeneous in patients with multiple lesions