Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration.

PURPOSE: To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. DESIGN: Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). METHODS: Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. RESULTS: Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. CONCLUSIONS: The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

An International Standard Set of Patient-Centered Outcome Measures After Stroke.

BACKGROUND AND PURPOSE: Value-based health care aims to bring together patients and health systems to maximize the ratio of quality over cost. To enable assessment of healthcare value in stroke management, an international standard set of patient-centered stroke outcome measures was defined for use in a variety of healthcare settings. METHODS: A modified Delphi process was implemented with an international expert panel representing patients, advocates, and clinical specialists in stroke outcomes, stroke registers, global health, epidemiology, and rehabilitation to reach consensus on the preferred outcome measures, included populations, and baseline risk adjustment variables. RESULTS: Patients presenting to a hospital with ischemic stroke or intracerebral hemorrhage were selected as the target population for these recommendations, with the inclusion of transient ischemic attacks optional. Outcome categories recommended for assessment were survival and disease control, acute complications, and patient-reported outcomes. Patient-reported outcomes proposed for assessment at 90 days were pain, mood, feeding, selfcare, mobility, communication, cognitive functioning, social participation, ability to return to usual activities, and health-related quality of life, with mobility, feeding, selfcare, and communication also collected at discharge. One instrument was able to collect most patient-reported subdomains (9/16, 56%). Minimum data collection for risk adjustment included patient demographics, premorbid functioning, stroke type and severity, vascular and systemic risk factors, and specific treatment/care-related factors. CONCLUSIONS: A consensus stroke measure Standard Set was developed as a simple, pragmatic method to increase the value of stroke care. The set should be validated in practice when used for monitoring and comparisons across different care settings.

Absolute MR thermometry using nanocarriers.

Accurate time-resolved temperature mapping is crucial for the safe use of hyperthermia-mediated drug delivery. We here propose a magnetic resonance imaging temperature mapping method in which drug delivery systems serve not only to improve tumor targeting, but also as an accurate and absolute nano-thermometer. This method is based on the temperature-dependent chemical shift difference between water protons and the protons in different groups of drug delivery systems. We show that the chemical shift of the protons in the ethylene oxide group in polyethylene glycol (PEG) is temperature-independent, whereas the proton resonance of water decreases with increasing temperature. The frequency difference between both resonances is linear and does not depend on pH and physiological salt conditions. In addition, we show that the proton resonance of the methyl group in N-(2-hydroxypropyl)-methacrylamide (HPMA) is temperature-independent. Therefore, PEGylated liposomes, polymeric mPEG-b-pHPMAm-Lac2 micelles and HPMA copolymers can provide a temperature-independent reference frequency for absolute magnetic resonance (MR) thermometry. Subsequently, we show that multigradient echo MR imaging with PEGylated liposomes in situ allows accurate, time-resolved temperature mapping. In conclusion, nanocarrier materials may serve as highly versatile tools for tumor-targeted drug delivery, acting not only as hyperthermia-responsive drug delivery systems, but also as accurate and precise nano-thermometers.

Influence of bone marrow composition on measurements of trabecular microstructure using decay due to diffusion in the internal field MRI: simulations and clinical studies.

PURPOSE: Decay due to diffusion in the internal field (DDIF) MRI allows for measurements of microstructures of porous materials at low spatial resolution and thus has potential for trabecular bone quality measurements. In trabecular bone, solid bone changes (osteoporosis) as well as changes in bone marrow composition occur. The influence of such changes on DDIF MRI was studied by simulations and in vivo measurements. METHODS: Monte Carlo simulations of DDIF in various trabecular bone models were conducted. Changes in solid bone and marrow composition were simulated with numerical bone erosion and marrow susceptibility variations. Additionally, in vivo measurements were performed in the lumbar spine of healthy volunteers aged 23-62 years. RESULTS: Simulations and in vivo results showed that 1) DDIF decay times decrease with increasing marrow fat and 2) the marrow fat percentage needs to be incorporated in the DDIF analysis to discriminate between healthy and osteoporotic solid bone structures. CONCLUSIONS: Bone marrow composition plays an important role in DDIF MRI: incorporation of marrow fat percentage into DDIF MRI allowed for differentiation of young and old age groups (in vivo experiments). DDIF MRI may develop into a means of assessing osteoporosis and disorders that affect marrow composition.

Temperature dependence of the magnetic volume susceptibility of human breast fat tissue: an NMR study.

OBJECT: Proton resonance frequency shift (PRFS)-based MR thermometry (MRT) is hampered by heat-induced susceptibility changes when applied in tissues containing fat, e.g., the human breast. In order to assess the impact of fat susceptibility changes on PRFS-based MRT during thermal therapy in the human breast, reliable knowledge of the temperature dependence of the magnetic volume susceptibility of fat, dχ(fat)/dT, is a prerequisite. In this work we have measured dχ(fat)/dT of human breast fat tissue, using a double-reference method to ensure invariance to temperature-induced changes in the proton electron screening constant. MATERIALS AND METHODS: Ex vivo measurements were taken on a 14.1 T five mm narrow bore NMR spectrometer. Breast fat tissue samples were collected from six subjects, directly postmortem. The susceptibility was measured over a temperature range from 24°C to 65°C. RESULTS: A linear behavior of the susceptibility over temperature was observed for all samples. The resulting dχ(fat)/dT of human breast fat ranged between 0.0039 and 0.0076 ppm/°C. CONCLUSION: It is concluded that the impact of heat-induced susceptibility changes of fat during thermal therapy in the breast may not be neglected.

Temperature-induced tissue susceptibility changes lead to significant temperature errors in PRFS-based MR thermometry during thermal interventions.

Proton resonance frequency shift-based MR thermometry (MRT) is hampered by temporal magnetic field changes. Temporal changes in the magnetic susceptibility distribution lead to nonlocal field changes and are, therefore, a possible source of errors. The magnetic volume susceptibility of tissue is temperature dependent. For water-like tissues, this dependency is in the order of 0.002 ppm/°C. For fat, it is in the same order of magnitude as the temperature dependence of the proton electron screening constant of water (0.01 ppm/°C). For this reason, proton resonance frequency shift-based MR thermometry in fatty tissues, like the human breast, is expected to be prone to errors. We aimed to quantify the influence of the temperature dependence of the susceptibility on proton resonance frequency shift-based MR thermometry. Heating experiments were performed in a controlled phantom set-up to show the impact of temperature-induced susceptibility changes on actual proton resonance frequency shift-based temperature maps. To study the implications for a clinical case, simulations were performed in a 3D breast model. Temperature errors were quantified by computation of magnetic field changes in the glandular tissue, resulting from susceptibility changes in a thermally heated region. The results of the experiments and simulations showed that the temperature-induced susceptibility changes of water and fat lead to significant errors in proton resonance frequency shift-based MR thermometry.

Absolute MR thermometry using time-domain analysis of multi-gradient-echo magnitude images.

MRI allows for absolute temperature measurements in substances containing two spectral resonances of which the frequency difference Delta f(T) is related to absolute temperature. This frequency difference can be extracted from spectroscopic data. An image-based MR technique that allows for the acquisition of spectroscopic data at high temporal and spatial resolution is the multi-gradient-echo sequence. In this work, the application of the multi-gradient-echo sequence for MR thermometry purposes was further developed. We investigated the possibility of postprocessing the multi-gradient-echo data into absolute temperature maps, using time-domain analysis of the magnitude of the multi-gradient-echo signals. In this approach, instead of an indirect computation of Delta f(T) from separately found frequencies, Delta f(T) is a direct output parameter. In vitro experiments were performed to provide proof of concept for retrieving absolute temperature maps from the time-domain analysis of multi-gradient-echo magnitude images. It is shown that this technique is insensitive to both field drift and local field disturbances. Furthermore, ex vivo bone marrow experiments were performed, using the fat resonance as a reference for absolute temperature mapping. It is shown that the postprocessing based on the magnitude signal in the time domain allows for the determination of Delta f(T) in bone marrow.

Do respiration and cardiac motion induce magnetic field fluctuations in the breast and are there implications for MR thermometry?

PURPOSE: To assess the distribution of respiration and cardiac motion-induced field fluctuations in the breast and to evaluate the implications of such fluctuations for proton resonance frequency shift (PRFS) MR thermometry in the breast. MATERIALS AND METHODS: Gradient echo MR field maps were made to study the effect of regular respiration, maximum capacity respiration, and cardiac motion on the stability of the local magnetic field in four healthy female volunteers. Field fluctuations (in parts-per-million [ppm]) were averaged over a region of interest covering both breasts. RESULTS: The average field fluctuation due to regular respiration was 0.13 ppm, due to maximum capacity respiration 0.16 ppm and <0.03 ppm due to cardiac motion. These fluctuations can be misinterpreted as temperature changes of 13, 16, and 3 degrees C when PRFS-based MR thermometry is used during thermal treatment of breast cancer. CONCLUSION: Respiration causes significant field fluctuations in the breast. If MR thermometry were to be safely used in clinical practice, these fluctuations should be taken into account and should probably be corrected for.