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A model-based planning tool, integrated in an imaging system, is envisioned for CT-guided percutaneous microwave ablation. This study aims to evaluate the biophysical model performance, by comparing its prediction retrospectively with the actualablation ground truth from a clinical data set in liver. The biophysical model uses a simplified formulation of heat depositionon the applicator and a heat sink related to vasculature to solve the bioheat equation. A performance metric is defined toassess how the planned ablation overlaps the actual ground truth. Results demonstrate superiority of this model predictioncompared to manufacturer tabulated data and a significant influence of the vasculature cooling effect. Nevertheless, vasculatureshortage due to branches occlusion and applicator misalignment due to registration error between scans affects the thermalprediction. With a more accurate vasculature segmentation, occlusion risk can be estimated, whereas branches can be usedas liver landmarks to improve the registration accuracy. Overall, this study emphasizes the benefit of a model-based thermalablation solution in better planning the ablation procedures. Contrast and registration protocols must be adapted to facilitate itsintegration into the clinical workflow.

PURPOSE: Magnetic Resonance Fingerprinting (MRF) with spiral readout enables rapid quantification of tissue relaxation times. However, it is prone to blurring due to off-resonance effects. Hence, fat blurring into adjacent regions might prevent identification of small tumors by their quantitative T1 and T2 values. This study aims to correct for the blurring artifacts, thereby enabling fast quantitative mapping in the female breast. METHODS: The impact of fat blurring on spiral MRF results was first assessed by simulations. Then, MRF was combined with 3-point Dixon water-fat separation and spiral blurring correction based on conjugate phase reconstruction. The approach was assessed in phantom experiments and compared to Cartesian reference measurements, namely inversion recovery (IR), multi-echo spin echo (MESE) and Cartesian MRF, by normalized root mean square error (NRMSE) and standard deviation (STD) calculations. Feasibility is further demonstrated in-vivo for quantitative breast measurements of 6 healthy female volunteers, age range 24-31 years. RESULTS: In the phantom experiment, the blurring correction reduced the NRMSE per phantom vial on average from 16% to 8% for T1 and from 18% to 11% for T2 when comparing spiral MRF to IR/MESE sequences. When comparing to Cartesian MRF, the NRMSE reduced from 15% to 8% for T1 and from 12% to 7% for T2. Furthermore, STDs decreased. In-vivo, the blurring correction removed fat bias on T1/T2 from a rim of about 7-8 mm width adjacent to fatty structures. CONCLUSION: The blurring correction for spiral MRF yields improved quantitative maps in the presence of water and fat., Submitted to Magnetic Resonance in Medicine. 13 pages, 7 figures, 3 tables

Smartphones have a large potential for improving data collection by using research apps and collecting sensor data. This brings opportunities to enhance or extend measurement and to simplify the response task for respondents. Sensor data can (partly) replace survey questions, and these sensors potentially generate better data than respondents can provide themselves. This seems very promising, but many methodological questions arise related to representation and measurement in smartphone surveys; are respondent willing and able to participate and share sensor data, and how useful are the additional data collected via sensors and apps? In this dissertation we investigated the effect of smartphone surveys in terms of reducing (or enlarging) error components. These errors can be divided into errors in the measurement and the representation. In Chapter 2 we perform a systematic review and meta-analysis to investigate how to improve the effectiveness of the consent to data linkage question. In Chapter 3 we study nonresponse and nonresponse bias in the smartphone-only version of the Dutch Time Use Survey (TUS). In Chapter 4 we focus on measurement error when collecting GPS data in a smartphone survey. In Chapter 5 we investigate both representation and measurement in an innovative and experimental study on the use of sensor data in fitness and health research.

Supplemental Material, Elevelt_Online_Appendix_A for Where You at? Using GPS Locations in an Electronic Time Use Diary Study to Derive Functional Locations by A. Elevelt, W. Bernasco, P. Lugtig, B. M. S. Ruiter and V. Toepoel in Social Science Computer Review

This abstract has been retracted at the request of the authors on May 19, 2021

Online surveys are increasingly completed on smartphones. There are several ways to structure online surveys so as to create an optimal experience for any screen size. For example, communicating through applications (apps) such as WhatsApp and Snapchat closely resembles natural turn-by-turn conversations between individuals. Web surveys currently mimic the design of paper questionnaires mostly, leading to a survey experience that may not be optimal when completed on smartphones. In this paper, we compare a research messenger design, which mimics a messenger app type of communication, to a responsive survey design. We investigate whether response quality is similar between the two designs and whether respondents’ satisfaction with the survey is higher for either version. Our results show no differences for primacy effects, number of nonsubstantive answers, and dropout rate. The length of open-ended answers was shorter for the research messenger survey compared to the responsive design, and the overall time of completion was longer in the research messenger survey. The evaluation at the end of the survey showed no clear indication that respondents liked the research messenger survey more than the responsive design. Future research should focus on how to optimally design online mixed-device surveys in order to increase respondent satisfaction and data quality.

Smartphones enable passive collection of sensor data alongside survey participation. Location data add context to people’s reports about their time use. In addition, linking global positioning system data to self-reported time use surveys (TUSs) can be valuable for understanding how people spend their time. This article investigates whether and how passive collection of geographical locations (coordinates) proves useful for deriving respondents’ functional locations. Participants of the ongoing Children of Immigrants Longitudinal Survey in the Netherlands were invited to participate in a TUS administered with a smartphone app that also unobtrusively tracked respondents’ locations. Respondents reported their activities per 10-min interval in a smartphone diary app ( n = 1,339) and shared their geographical location data ( n = 1,264). The correspondence between the functional locations derived from the time use data and those derived from the geographical location data was assessed by calculating the percentage of intervals in which both measures are similar. Overall, results show that home locations can be automatically assigned reliably but that respondent information is required to reliably assign work or school locations. In addition, location tracking data contain many measurement errors, making it difficult to record valid locations. Multilevel models show that the variability in correct classifications is intrapersonal and largely predicted by phone type, which determines location measurement frequency.

The increasing use of smartphones opens up opportunities for novel ways of survey data collection, but also poses new challenges. Collecting more and different types of data means that studies can become increasingly intrusive. We risk over-asking participants, leading to nonresponse. This study documents nonresponse and nonresponse bias in a smartphone-only version of the Dutch Time Use Survey (TUS). Respondents from the Dutch LISS panel were asked to perform five sets of tasks to complete the whole TUS: 1) accept an invitation to participate in the study and install an app, 2) fill out a questionnaire on the web, 3) participate in the smartphone time use diary on their smartphone, 4) answer pop-up questions and 5) give permission to record sensor data (GPS locations and call data). Results show that 42.9% of invited panel members responded positively to the invitation to participate in a smartphone survey. However, only 28.9% of these willing panel members completed all stages of the study. Predictors of nonresponse are somewhat different at every stage. In addition, respondents who complete all smartphone tasks are different from groups who do not participate at some or any stage of the study. By using data collected in previous waves we show that nonresponse leads to nonresponse bias in estimates of time use. We conclude by discussing implications for using smartphone apps in survey research., Survey Research Methods, Vol 13 No 2 (2019)

High Intensity Focused Ultrasound (HIFU) is a non invasive therapeutic method, which has been a subject of interest for the treatment of various kinds of tumors. Despite the numerous advantages, HIFU techniques do not reach the high delivery precision like other therapies (e.g., radiotherapy). For this reason, a correct therapy planning and monitoring in HIFU treatments remains a challenge. We propose HIFUpm, a visual analytics approach which enables the visualization of the HIFU simulation results, while guiding the user in the evaluation of the procedure. We illustrate the use of HIFUpm for an ablative treatment of an osteoid osteoma. This use case demonstrates that HIFUpm provides a flexible visual environment to plan and monitor HIFU procedures., Eurographics Workshop on Visual Computing for Biology and Medicine, Animation, Tracking, and Simulations, 207, 211, Daniela Modena, Davide Bassano, Aaldert Elevelt, Marco Baragona, Peter A. J. Hilbers, and Michel A. Westenberg

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR-HIFU treatments.

Objectives: Bone pain resulting from cancer metastases reduces a patient's quality of life. Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) is a promising alternative palliative thermal treatment technique for bone metastases that has been tested in a few clinical studies. Here, we describe a comprehensive pre-clinical study to investigate the effects, and efficacy of MR-HIFU ablation for the palliative treatment of osteoblastic bone metastases in rats. Materials and methods: Prostate cancer cells (MATLyLu) were injected intra-osseously in Copenhagen rats. Upon detection of pain, as determined with a dynamic weight bearing (DWB) system, a MR-HIFU system was used to thermally ablate the bone region with tumor. Treatment effect and efficacy were assessed using magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) with technetium-99m medronate (99mTc-MDP), micro-computed tomography (μCT) and histology. Results: DWB analysis demonstrated that MR-HIFU-treated animals retained 58.6±20.4% of limb usage as compared to 2.6±6.3% in untreated animals (P=0.003). MR-HIFU delayed tumor specific growth rates (SGR) from 29±6 to 13±5%/day (P3) had a greater accumulation of 99mTc-MDP than HIFU-treated animals (127.0±42.7mm3, P=0.004). The total bone volume increase for untreated and HIFU-treated animals was 15.6±9.6% and 3.0±4.1% (P=0.004), respectively. Histological analysis showed ablation of nerve fibers, tumor, inflammatory and bone cells. Conclusions: Our study provides a detailed characterization of the effects of MR-HIFU treatment on bone metastases, and provides fundamental data, which may motivate and advance its use in the clinical treatment of painful bone metastases with MR-HIFU.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) is a noninvasive thermal technique that enables rapid heating of a specific area in the human body. Its clinical relevance has been proven for the treatments of soft tissue tumors, like uterine fibroids, and for the treatments of solid tumors in bone. In MR-HIFU treatment, MR-thermometry is used to monitor the temperature evolution in soft tissue. However, this technique is currently unavailable for bone tissue. Computer models can play a key role in the accurate prediction and monitoring of temperature. Here, we present a computer ray tracing model that calculates the heat production density in the focal region. This model accounts for both the propagation of shear waves and the interference between longitudinal and shear waves. The model was first compared with a finite element approach which solves the Helmholtz equation in soft tissue and the frequency-domain wave equation in bone. To obtain the temperature evolution in the focal region, the heat equation was solved using the heat production density generated by the raytracer as a heat source. Then, we investigated the role of the interaction between shear and longitudinal waves in terms of dissipated power and temperature output. The results of our model were in agreement with the results obtained by solving the Helmholtz equation and the frequency-domain wave equation, both in soft tissue and bone. Our results suggest that it is imperative to include both shear waves and their interference with longitudinal waves in the model when simulating high intensity focused ultrasound propagation in solids. In fact, when modeling HIFU treatments, omitting the interference between shear and longitudinal waves leads to an over-estimation of the temperature increase in the tissues.

Objectives: The aim of this study was to investigate the intratumoral distribution of a temperature-sensitive liposomal carrier and its encapsulated compounds, doxorubicin, and a magnetic resonance (MR) imaging contrast agent after high-intensity focused ultrasound (HIFU)-mediated hyperthermia-induced local drug release. Materials and Methods: In-111-labeled temperature-sensitive liposomes encapsulating doxorubicin and [Gd(HPDO3A) (H2O)] were injected intravenously in the tail vein of rats (n = 12) bearing a subcutaneous rhabdomyosarcoma tumor on the hind leg. Immediately after the injection, local tumor hyperthermia (2 x 15 minutes) was applied using a clinical 3 T MR-HIFU system. Release of [Gd(HPDO3A) (H2O)] was studied in vivo by measuring the longitudinal relaxation rate R-1 with MR imaging. The presence of the liposomal carriers and the intratumoral distribution of doxorubicin were imaged ex vivo with autoradiography and fluorescence microscopy, respectively, for 2 different time points after injection (90 minutes and 48 hours). Results: In hyperthermia-treated tumors, radiolabeled liposomes were distributed more homogeneously across the tumor than in the control tumors (coefficient of variation(hyp, 90 min) = 0.7 +/- 0.2; coefficient of variation(cntrl, 90 min) = 1.1 +/- 0.2). At 48 hours after injection, the liposomal accumulation in the tumor was enhanced in the hyperthermia group in comparison with the controls. A change in R-1 was observed in the HIFU-treated tumors, suggesting release of the contrast agent. Fluorescence images showed perivascular doxorubicin in control tumors, whereas in the HIFU-treated tumors, the delivered drug was spread over a much larger area and also taken up by tumor cells at a larger distance from blood vessels. Conclusions: Treatment with HIFU hyperthermia not only improved the immediate drug delivery, bioavailability, and intratumoral distribution but also enhanced liposomal accumulation over time. The sum of these effects may have a significant contribution to the therapeutic outcome.

To compare respiratory-triggered inversion-recovery (IR) gradient- and spin-echo (GRASE) magnetic resonance (MR) imaging with respiratory-triggered T2-weighted fast spin-echo (SE) imaging in the diagnosis of liver metastases.In this prospective study, two radiologists independently identified focal hepatic lesions on respiratory-triggered IR GRASE and respiratory-triggered fast SE MR images in 28 consecutive patients with 186 (135 malignant and 51 benign) proved lesions. A combination of findings at surgery, intraoperative ultrasonography (US), and histologic examination served as the standard of reference. Contrast-to-noise ratios (CNRs) were obtained from 86 lesions larger than 10 mm.The sensitivity in the detection of liver metastases was, independent of lesion size and observer, higher for IR GRASE imaging (55%) than for fast SE imaging (44%-50%) (observer 1, P = .014; observer 2, P = .21). Confidence levels with IR GRASE imaging were higher, but not significantly so, than those with fast SE imaging (P.098). Both observers characterized liver lesions better with IR GRASE than with fast SE imaging (observer 1, P = .04; observer 2, P = .48). The metastasis-liver CNR was significantly higher (P = .012) with IR GRASE imaging.The respiratory-triggered IR GRASE sequence is a fast alternative to the respiratory-triggered fast SE sequence in the evaluation of suspected liver metastases.

PURPOSE To compare spiral CT and MRT for the detection of focal pulmonary lesions. PATIENTS AND METHODS 50 patients with focal pulmonary lesions confirmed by spiral CT were examined using a T2-weighted UTSE sequence (TE: 90 ms, TR: 1500-3000 ms, echo interval 9 ms, 8 mm slice thickness, diastolic triggering, expiratory breath gating). Image quality was compared using a 4-stage scale. Lesions with a minimum size of 2 mm were counted and measured in the CT image. The results were compared with the MRT images. RESULTS The image quality in CT examinations with an average value of 1.22 better than that in MRT (1.78). In total 163 pulmonary lesions with a size of 2-115 mm were found by CT. MRT found 151/163 lesions (92.6%). Of the 12 lesions not detected, 9 were smaller than 4 mm, 1 corresponded to a 12 mm large, completely calcified granuloma. In 2 cases there was a 4 or 5 mm large unspecific scar. Thus, 160/163 (98.1%) of all lesions larger than 3 mm were detected. CONCLUSIONS MRT with use of a suitable UTSE sequence is an alternative to CT for the detection of focal pulmonary lesions with a size larger than 3 mm.

Objectives The purpose of this study was to investigate the use of Gd-DTPA shortly before magnetic resonance guided high-intensity focused ultrasound MR-HIFU thermal ablation therapy with respect to dissociation, trapping, and long-term deposition of gadolinium (Gd) in the body. Materials and methods Magnetic resonance-HIFU ablation treatment was conducted in vivo on both rat muscle and subcutaneous tumor (9L glioma) using a clinical 3T MR-HIFU system equipped with a small-animal coil setup. A human equivalent dose of gadopentetate dimeglumine (Gd-DTPA) (0.6 mmol/kg of body weight) was injected via a tail vein catheter just before ablation (≤5 minutes). Potential trapping of the contrast agent in the ablated area was visualized through the acquisition of R1 maps of the target location before and after therapy. The animals were sacrificed 2 hours or 14 days after the injection (n = 4 per group, a total of 40 animals). Subsequently, the Gd content in the tissue and carcass was determined using inductively coupled plasma techniques to investigate the biodistribution. Results Temporal trapping of Gd-DTPA in the coagulated tissue was observed on the R1 maps acquired within 2 hours after the ablation, an effect confirmed by the inductively coupled plasma analysis (3 times more Gd was found in the treated muscle volume than in the control muscle tissue). Two weeks after the therapy, the absolute amount of Gd present in the coagulated tissue was low compared with the amount present in the kidneys 14 days after the injection (ablated muscle, 0.009% ± 0.002% ID/g; kidney, 0.144% ± 0.165% ID/g). There was no significant increase in Gd content in the principal target organs for translocated Gdions (liver, spleen, and bone) or in the entire carcasses between the HIFU- and sham-treated animals. Finally, an in vivo relaxivity of 4.6 mmols was found in the HIFU-ablated volume, indicating intact Gd-DTPA. Conclusions Magnetic resonance-HIFU treatment does not induce the dissociation of Gd-DTPA. In small-tissue volumes, no significant effect on the long-term in vivo Gd retention was found. However, care must be taken with the use of proton resonance frequency shift-based MR thermometry for HIFU guidance in combination with Gd because the susceptibility artifact induced by Gd can severely influence treatment outcome.