Assessing response in breast cancer with dynamic contrast-enhanced magnetic resonance imaging: are signal intensity-time curves adequate?

Quantitative DCE-MRI parameters including K(trans) (transfer constant min(-1)) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity-time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K(trans) to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K(trans) values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17-86 mm) at baseline and 26 mm (range 10-85 mm) after two cycles of NAC. Median baseline K(trans) (min(-1)) was 0.214 (range 0.085-0.469), and post-two cycles of NAC was 0.128 (range 0.013-0.603). SITC shapes were significantly related to K(trans) values both before (χ (2) = 43.3, P = 0.000) and after two cycles of NAC (χ (2) = 60.5, P = 0.000). Changes in curve shapes were significantly related to changes in K(trans) (χ (2) = 53.5, P = 0.000). Changes in curve shape were significantly correlated with clinical (P = 0.005) and pathological response (P = 0.005). Reductions in curve shape of ≥1 point were significant for overall improved survival using Kaplan-Meier analysis with a 5-year OS of 80.9 versus 68.6 % (P = 0.048). SITCs require no special software to generate and provide a useful method of assessing the effectiveness of NAC for primary breast cancer.

Radiation dose from volumetric helical perfusion CT of the thorax, abdomen or pelvis.

PURPOSE: To evaluate the radiation doses delivered during volumetric helical perfusion CT of the thorax, abdomen or pelvis. MATERIALS AND METHODS: The dose-length product (DLP) and CT dose index (CTDIvol) were recorded and effective dose (E) determined for patients undergoing CT (4D adaptive spiral) for tumour evaluation. Image noise and contrast to noise (CNR) at peak enhancement were also assessed for quality. RESULTS: Forty two consecutive examinations were included: thorax (16), abdomen (10), pelvis (16). Z-axis coverage ranged from 11.4 to 15.7 cm. Mean DLP was 1288.8 mGy.cm (range: 648 to 2456 mGy.cm). Mean CTDIvol was 96.2 mGy (range: 32.3 to 169.4 mGy). Mean effective dose was 19.6 mSv (range: 12.3 mSv to 36.7 mSv). In comparison mean DLP and effective dose was 885.2 mGy.cm (range: 504 to 1633 mGy.cm) and 13.3 mSV (range: 7.8 to 24.5 mSv) respectively for the standard staging CT thorax, abdomen and pelvis. Mean tumour CNR at peak enhancement was 1.87. CONCLUSION: The radiation dose imposed by perfusion CT was on average 1.5 times that of a CT thorax, abdomen and pelvis. The dose is not insubstantial, and must be balanced by the potential clinical utility of additional physiologic data. Further efforts towards dose reduction should be encouraged.

Modeling the basin of attraction as a two-dimensional manifold from experimental data: applications to balance in humans.

We present a method of modeling the basin of attraction as a three-dimensional function describing a two-dimensional manifold on which the dynamics of the system evolves from experimental time series data. Our method is based on the density of the data set and uses numerical optimization and data modeling tools. We also show how to obtain analytic curves that describe both the contours and the boundary of the basin. Our method is applied to the problem of regaining balance after perturbation from quiet vertical stance using data of an elite athlete. Our method goes beyond the statistical description of the experimental data, providing a function that describes the shape of the basin of attraction. To test its robustness, our method has also been applied to two different data sets of a second subject and no significant differences were found between the contours of the calculated basin of attraction for the different data sets. The proposed method has many uses in a wide variety of areas, not just human balance for which there are many applications in medicine, rehabilitation, and sport.

Competencies and training of radiographers and technologists for PET/MR imaging - a study from the UK MR-PET network.

BACKGROUND: After the success of PET/CT as a clinical diagnostic tool, the introduction of PET/MRI is a natural development aimed at further improving combined diagnostic imaging and reduced ionising radiation dose for half-body imaging. As with PET and CT, the combination of PET and MRI presents a series of issues that need to be addressed regarding workforce training and education. At present, there is a lack of agreement over the competencies, training requirements and educational pathways needed for PET/MRI operation. In the UK, following the establishment of the MR-PET imaging network, a task force was created to investigate the status of the workforce training, identify gaps and make recommendations regarding staff training. To do this, we ran a national survey on the status of the workforce training and the local practices across the UK's seven PET/MRI sites, reviewed the literature, and convened a panel of experts, to assess all the evidence and make recommendations regarding PET/MRI competencies and training of nuclear medicine technologists and radiographers. RESULTS: There is limited literature available specifically on competencies and training for technologists and radiographers. The recommendations on the topic needed revisiting and adapting to the UK MR-PET network. The online survey confirmed the need for developing PET/MRI competencies and training pathways. Local organisational structures and practices were shared across the seven sites, based on models derived from experience outside the UK. The panel of experts agreed on the need for PET/MRI competencies and training strategies. Professional organisations started collaborative discussions with partners from both Nuclear Medicine and Radiography to set training priorities. Multidisciplinary collaboration and partnership were suggested as a key to a successful implementation of competencies and training. CONCLUSIONS: The report identified the need for establishing competencies for the PET/MRI workforce, particularly for technologists and radiographers. It also helped defining these competencies as well as identifying the demand for bespoke training and the development of local and national courses to be implemented to fulfil this new training need.

Type of delivery is not affected by light resistance and toning exercise training during pregnancy: a randomized controlled trial.

OBJECTIVE: We examined the effect of light-intensity resistance exercise training that is performed during the second and third trimester of pregnancy by previously sedentary and healthy women on the type of delivery and on the dilation, expulsion, and childbirth time. STUDY DESIGN: We randomly assigned 160 sedentary women to either a training (n=80) or a control (n=80) group. We recorded several maternal and newborn characteristics, the type of delivery (normal, instrumental, or cesarean), and dilation, expulsion, and childbirth time. RESULTS: The percentage of women who had normal, instrumental, or cesarean delivery was similar in the training (70.8%, 13.9%, and 15.3%, respectively) and control (71.4%, 12.9%, and 15.7%, respectively) groups. The mean dilation, expulsion, and childbirth time did not differ between groups. CONCLUSION: Light-intensity resistance training that is performed over the second and third trimester of pregnancy does not affect the type of delivery.

Correlations between the blood pressure and other health variables in Spanish adolescents.

The aim of this paper was to study the correlations between blood pressure and other health variables in Spanish adolescents. 204 boys and 270 girls (aged 13-17 years, with written parental consent,) from 18 private and 17 public educative centers from 16 of 21 districts of the city of Madrid, constituted the representative sample. 12.7% of the boys and 35.6% of the girls were inactive or sedentary. Socioeconomic status significantly determined the physical activity of girls, especially in the age group 16-17 years. The tobacco consumption by girls was significantly greater than by boys. A significant inverse relation of tobacco consumption with physical activity was found for boys. Among the girls, 47.4% were lightly overweight to obese as opposed to 14.7% of boys. A significant association between adiposity and physical activity in the girls was observed. The averages for the systolic/diastolic blood pressure were 125.6/71.3 mm Hg in boys and 118/69.4 mm Hg in girls. A significant relation between gender and systolic blood pressure was found. A relation between physical activity and diastolic blood pressure for boys was observed (69.9 mm Hg for active or very active and 74.1 mm Hg for moderately active to sedentary). The lack of existing relations between blood pressure and others variables support the hypothesis that these variables require a longer-term to become obvious cardiovascular risk factors. We believe, therefore, that girls and those from lower socioeconomic status should receive high-priority attention concerning health-related habits.

Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry.

BACKGROUND: Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted 'gold standards' of tumour biology such as immunohistochemical measures is not established. METHODS: A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation. RESULTS: Hypoxia-inducible factor-1α was correlated with first-order kurtosis (r = -0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness (r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis (r = -0.52, P = .047), fractal dimension (r = 0.613, P = .015), and lacunarity (r = -0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity (r = 0.547, P = .035). CONCLUSIONS: The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.

UK quantitative WB-DWI technical workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion-weighted imaging for cancer.

OBJECTIVE: Application of whole body diffusion-weighted MRI (WB-DWI) for oncology are rapidly increasing within both research and routine clinical domains. However, WB-DWI as a quantitative imaging biomarker (QIB) has significantly slower adoption. To date, challenges relating to accuracy and reproducibility, essential criteria for a good QIB, have limited widespread clinical translation. In recognition, a UK workgroup was established in 2016 to provide technical consensus guidelines (to maximise accuracy and reproducibility of WB-MRI QIBs) and accelerate the clinical translation of quantitative WB-DWI applications for oncology. METHODS: A panel of experts convened from cancer centres around the UK with subspecialty expertise in quantitative imaging and/or the use of WB-MRI with DWI. A formal consensus method was used to obtain consensus agreement regarding best practice. Questions were asked about the appropriateness or otherwise on scanner hardware and software, sequence optimisation, acquisition protocols, reporting, and ongoing quality control programs to monitor precision and accuracy and agreement on quality control. RESULTS: The consensus panel was able to reach consensus on 73% (255/351) items and based on consensus areas made recommendations to maximise accuracy and reproducibly of quantitative WB-DWI studies performed at 1.5T. The panel were unable to reach consensus on the majority of items related to quantitative WB-DWI performed at 3T. CONCLUSION: This UK Quantitative WB-DWI Technical Workgroup consensus provides guidance on maximising accuracy and reproducibly of quantitative WB-DWI for oncology. The consensus guidance can be used by researchers and clinicians to harmonise WB-DWI protocols which will accelerate clinical translation of WB-DWI-derived QIBs.

Feasibility of simultaneous PET-MR perfusion using a novel cardiac perfusion phantom.

BACKGROUND: PET-MR scanners are beginning to be employed for quantitative myocardial perfusion imaging. In order to examine simultaneous perfusion calculations, this work describes a feasibility study of simultaneous PET-MR of gadolinium-based contrast agent (GBCA) and PET radiotracer in a novel cardiac perfusion phantom. RESULTS: [18F]F- and GBCA were injected simultaneously into a cardiac phantom using a range of ground-truth myocardial perfusion rates of 1 to 5 ml/g/min. PET quantification of K1 (ml/g/min) was performed using a single tissue compartment model. MR perfusion was calculated using a model-independent signal deconvolution technique. PET and MR signal traces from the phantom aorta and myocardial sections show true simultaneous PET and MR arterial input functions (AIF) and myocardial uptake respectively at each perfusion rate. Calculation of perfusion parameters showed both K1 and h(t = 0) (PET and MR perfusion parameters respectively) to be linearly related with the ground truth perfusion rate (PT ), and also linearly related to each other (R2 = 0.99). The highest difference in perfusion values between K1 and PT was 16% at 1 ml/g/min, and the mean difference for all other perfusion rates was <3%. CONCLUSIONS: The perfusion phantom allows accurate and reproducible simulation of the myocardial kinetics for simultaneous PET-MR imaging, and may find use in protocol design and development of PET-MR based quantification techniques and direct comparison of quantification of the two modalities.

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia.

OBJECTIVE: Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner. METHODS: Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time. RESULTS: SUVmax exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms. CONCLUSION: Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are consistent with other published studies however more specimens are required for full validation.

PET/MRI in Oncological Imaging: State of the Art.

Positron emission tomography (PET) combined with magnetic resonance imaging (MRI) is a hybrid technology which has recently gained interest as a potential cancer imaging tool. Compared with CT, MRI is advantageous due to its lack of ionizing radiation, superior soft-tissue contrast resolution, and wider range of acquisition sequences. Several studies have shown PET/MRI to be equivalent to PET/CT in most oncological applications, possibly superior in certain body parts, e.g., head and neck, pelvis, and in certain situations, e.g., cancer recurrence. This review will update the readers on recent advances in PET/MRI technology and review key literature, while highlighting the strengths and weaknesses of PET/MRI in cancer imaging.

Geometry and transport in a model of two coupled quadratic nonlinear waveguides.

This paper applies geometric methods developed to understand chaos and transport in Hamiltonian systems to the study of power distribution in nonlinear waveguide arrays. The specific case of two linearly coupled chi((2)) waveguides is modeled and analyzed in terms of transport and geometry in the phase space. This gives us a transport problem in the phase space resulting from the coupling of the two Hamiltonian systems for each waveguide. In particular, the effect of the presence of partial and complete barriers in the phase space on the transfer of intensity between the waveguides is studied, given a specific input and range of material properties. We show how these barriers break down as the coupling between the waveguides is increased and what the role of resonances in the phase space has in this. We also show how an increase in the coupling can lead to chaos and global transport and what effect this has on the intensity.

Dynamic MRI for imaging tumor microvasculature: comparison of susceptibility and relaxivity techniques in pelvic tumors.

PURPOSE: To assess the reproducibility of intrinsic relaxivity and both relaxivity- and susceptibility-based dynamic contrast enhanced (DCE) MRI in pelvic tumors; to correlate kinetic parameters obtained and to assess whether acute antivascular effects are seen in response to cisplatin- or taxane-based chemotherapy. MATERIALS AND METHODS: T1-weighted and T2*-weighted DCE-MRI and basal R2* measurements were performed on three consecutive days in women with gynecological tumors. The third scan was 21.0 (range 17.3-23.5) hours after the first cycle of chemotherapy. Kinetic parameter estimates were obtained and correlated between techniques. Test-retest reproducibility and response to treatment were assessed. RESULTS: Relative blood volume (rBV) and relative blood flow (rBF) correlated strongly with transfer constant (Ktrans), kep, and the initial area under the gadopentetate dimeglumine (Gd-DTPA) concentration-time curve (IAUGC) (all P<0.01). The group 95% confidence interval (CI) for change was -10.8 to +12.1%; +/-5.1%; -9.5 to +10.5%; +/-7.5%; for Ktrans, ve, kep, and IAUGC, respectively, and +/-13.6%, +/-2.4%, +/-11.6%, and +/-11.0%, for rBV, mean transit time (MTT), rBF, and R2*, respectively. There were no significant acute changes in kinetic parameter estimates in response to treatment on group analysis, apart from a small decrease in ve. CONCLUSION: The results confirm the dominant influence of flow on Ktrans in untreated gynecological tumors. There is no evidence of an acute, large magnitude antivascular effect caused by cisplatin- or taxane-based chemotherapy.