Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives.

Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly.

Estimate of FDG excretion by means of compartmental analysis and ant colony optimization of nuclear medicine data.

[(18)F]fluoro-2-deoxy-D-glucose (FDG) is one of the most utilized tracers for positron emission tomography (PET) applications in oncology. FDG-PET relies on higher glycolytic activity in tumors compared to normal structures as the basis of image contrast. As a glucose analog, FDG is transported into malignant cells which typically exhibit an increased radioactivity. However, different from glucose, FDG is not reabsorbed by the renal system and is excreted to the bladder. The present paper describes a novel computational method for the quantitative assessment of this excretion process. The method is based on a compartmental analysis of FDG-PET data in which the excretion process is explicitly accounted for by the bladder compartment and on the application of an ant colony optimization (ACO) algorithm for the determination of the tracer coefficients describing the FDG transport effectiveness. The validation of this approach is performed by means of both synthetic data and real measurements acquired by a PET device for small animals (micro-PET). Possible oncological applications of the results are discussed in the final section.

Metformin temporal and localized effects on gut glucose metabolism assessed using 18F-FDG PET in mice.

UNLABELLED: In the course of metformin treatment, staging abdominal cancer lesions with (18)F-FDG PET images is often hindered by the presence of a high bowel radioactivity. The present study aimed to verify the mechanism underlying this phenomenon. METHODS: Fifty-three mice were submitted to dynamic acquisitions of (18)F-FDG kinetics under fasting conditions. Three small-animal PET scans were obtained over a 4-mo study period. The animals were subdivided into 4 groups according to the following metformin administration protocol: group 1, untreated mice (n = 15); group 2, mice exposed to metformin treatment (750 mg/kg/d) for the 48 h before each PET study (pulsed, n = 10); group 3, mice treated for the whole study period (prolonged, n = 10); and group 4, mice in which prolonged treatment was interrupted 48 h before PET (interrupted, n = 8). The rate constant of (18)F-FDG uptake was estimated by Patlak analysis. At the end of the study, the ileum and colon were harvested, washed, and counted ex vivo. Two further groups, of 5 animals each, were included to evaluate the effect of prolonged metformin treatment on phosphorylated adenosine monophosphate (AMP)-activated protein kinase (pAMPK) form and gene expression for thioredoxin-interacting protein (TXNIP). RESULTS: Pulsed treatment did not modify gut tracer retention with respect to the untreated group. Conversely, prolonged treatment induced a progressive increase in (18)F-FDG uptake that selectively involved the colonic wall, without any significant contamination of bowel content. This effect persisted after a complete drug washout in the interrupted group. These responses were paralleled by increased pAMPK availability and by reduced expression of TXNIP messenger RNA in colonic enterocytes exposed to prolonged metformin treatment. CONCLUSION: Metformin causes a selective increase in colonic (18)F-FDG uptake. This effect appears after a relatively long period of treatment and persists soon after drug washout. Accordingly, the increased bowel glucose metabolism reflects a biologic response to chronic metformin treatment characterized by increased levels of pAMPK and reduced levels of TXNIP.

An optimisation approach to multiprobe cryosurgery planning.

In cryosurgery operations, tumoural cells are killed by means of a freezing procedure realised with the insertion of cryoprobes in the diseased tissue. Cryosurgery planning aims at establishing the best values for operation parameters like number and position of the probes or temperature and duration of the freezing process. Here, we present an application of ant colony optimisation (ACO) to cryosurgery planning, whereby the ACO cost function is computed by numerically solving several direct Stefan problems in biological tissues. The method is validated in the case of a 2D phantom of a prostate cross section.

Intrabone transplant of cord blood stem cells establishes a local engraftment store: a functional PET/FDG study.

BACKGROUND: Despite advancements in comprehension of molecular mechanisms governing bone marrow (BM) homing of hematopoietic stem cells, cord blood transplant (CBT) suffers from a slow rate of hematopoietic recovery. Intrabone (i.b.) injection has been proposed as a method able to improve speed of BM engraftment with respect to conventional i.v. protocols. However, the mechanisms underlying this benefit are largely unknown. AIM: To verify whether i.b.-CBT determines a local engraftment able to predict the reconstitution of recipient hematopoiesis. DESIGN AND METHODS: Twenty-one patients with hematologic malignancies received i.b. injection into both iliac crests of 3.2 ± 0.68 ∗ 107/kg cord blood cells. One month following i.b.-CBT, PET-CT imaging was performed. Maximal standardized uptake values (SUVs) were assessed in BM of both iliac crests and in all lumbar vertebrae. RESULTS: Maximal SUV within iliac crests was higher than in lumbar vertebrae (4.1 ± 1.7 versus 3.2 ± 0.7, resp., P = 0.01). However, metabolic activity in these two different BM districts was significantly correlated (r = 0.7, P < 0.001). Moreover, FDG uptake values within the injection site closely predicted platelet recovery 100 days after i.b.-CBT (r = 0.72, P < 0.01). CONCLUSIONS: The metabolic activity of injected BM predicts the subsequent rate of hematopoietic recovery after i.b.-CBT, suggesting a pivotal role of the local engraftment in the reconstitution of recipient hematopoiesis.

Estimating the whole bone-marrow asset in humans by a computational approach to integrated PET/CT imaging.

PURPOSE: Despite their relevance in clinical medicine, the extension and activity of the bone marrow (BM) cannot be directly evaluated in vivo. We propose a new method to estimate these variables by combining structural and functional maps provided by CT and PET. METHODS: BM extension and glucose uptake were estimated in 102 patients undergoing whole-body PET/CT because of a history of nonmetastatic melanoma. Image analysis assumed that the BM is surrounded by compact bone. An iterative optimization scheme was applied to each CT slice to identify the external border of the bone. To identify compact bone, the algorithm measured the average Hounsfield coefficient within a two-pixel ring located just inside the bone contour. All intraosseous pixels with an attenuation coefficient lower than this cut-off were flagged as 1, while the remaining pixels were set at 0. Binary masks created from all CT slices were thus applied to the PET data to determine the metabolic activity of the intraosseous volume (IBV). RESULTS: Estimated whole-body IBV was 1,632 ± 587 cm(3) and was higher in men than in women (2,004 ± 498 cm(3) vs. 1,203 ± 354 cm(3), P < 0.001). Overall, it was strictly correlated with ideal body weight (r = 0.81, P = 0.001) but only loosely with measured body weight (r = 0.43, P = 0.01). The average FDG standardized uptake value (SUV) in the thoracic and lumbar vertebrae was 2.01 ± 0.36, Accordingly, intraosseous voxels with SUV ≥ 1.11 (mean spine SUV - 2.5 × SD) were considered as active "red" BM and those with SUV <1.11 as "yellow" BM. Estimated red BM volume was 541 ± 195 ml, with a higher prevalence in the axial than in the appendicular skeleton (87 ± 8 % vs. 10 ± 8 %, P < 0.001). Again, red BM volume was higher in men than in women (7.8 ± 2.2 vs. 6.7 ± 2.1 ml/kg body weight, P < 0.05), but in women it occupied a greater fraction of the IBV (32 ± 7 % vs. 36 ± 10 %, P < 0.05). Patient age modestly predicted red BM SUV, while it was robustly and inversely correlated with red BM volume. CONCLUSION: Our computational analysis of PET/CT images provides a first estimation of the extension and metabolism of the BM in a population of adult patients without haematooncological disorders. This information might represent a new window to explore pathophysiology the BM and the response of BM diseases to chemotherapy.

Application of the no-sampling linear sampling method to breast cancer detection.

In this paper, the no-sampling linear sampling method is applied to microwave imaging of cancerous tissues in realistic models of female breast obtained from magnetic resonance imaging (MRI). The adopted formulation is based on a modified version of the far-field equation, sensitive to anomalies with respect to the healthy breast. The healthy configuration is taken into account through the related Green's function, which is numerically computed. The adopted imaging technique is assessed against the inspection of tumors of several positions and sizes in noisy environments. Moreover, a numerical analysis of the robustness of the method is performed when the model parameters used for evaluating the Green's function are not exactly known.