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Caren Marzban

Limited Term Appointment - Pro Staff

Lecturer, Statistics

Email

marzban@apl.washington.edu

Education

B.S. Physics, Michigan State University, 1981

Ph.D. Theoretical Physics, University of North Carolina, 1988

Publications

2000-present and while at APL-UW

Low-intensity focused ultrasound alters Alzheimer's disease pathology, in vivo, as a function of ultrasound dose and age

Phutirat, A., K.A. Culevski, H. Mach, J. Kwon, H. Tan, G. Koh, C. Marzban, and P.D. Mourad, "Low-intensity focused ultrasound alters Alzheimer's disease pathology, in vivo, as a function of ultrasound dose and age," Brain Sci., 16, doi:10.3390/brainsci16070757, 2026.

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18 Jul 2026

Alzheimer’s Disease (AD) and vascular dementia contribute up to ~75% of dementia cases, as determined via autopsy. AD arises in part due to the buildup of aberrant proteins (amyloid beta (Aβ) and Tau); vascular dementia is caused by reduced cerebral blood flow. Each dementia mechanisms damages brain. Bobola et al. found that their low-intensity focused ultrasound (FUS) protocol applied to the brains of the 5XFAD mouse model of AD reduced Aβ by 50% through activation of microglia. Eguchi et al. found that their own FUS protocol applied to the brains of the same mouse model reduced Aβ by 15% and increased cerebral blood flow by 50% through an increase in endothelial nitric oxide synthase (eNOS). Here, we sought to test a combined version of those two FUS protocols, expecting both a decrease in Aβ burden and an increase in eNOS.

Using a diagnostic ultrasound probe, we applied our combined FUS protocol primarily to the left hippocampus of anesthetized 5XFAD mice, for an hour a day, for three days for younger mice and for five days for older mice. On day three or five, respectively, we harvested their brains and performed histological analysis to assess Aβ burden, microglial activation and their co-localization with Aβ, as well as the burden of eNOS within neuronal nuclei (here called intra-neuronal eNOS) and outside of neurons.

Relative to untreated mice, the treated younger mice had more activated microglia co-localized with Aβ and reduced Aβ burden for large plaques, as well as no change in each measure of eNOS. In contrast, the treated older AD mice had no change in activated microglia co-localized with Aβ, and no change in Aβ burden. However, relative to untreated older AD mice, FUS decreased total and extra-neuronal eNOS and increased intra-neuronal eNOS.

The ability of our FUS protocol to reduce Aβ burden and alter the eNOS distribution depends critically upon the age of the AD mice (more Aβ plaques for a comparable number of microglia for older mice relative to younger mice) and duration of the treatment. The observed decrease in extra-neuronal eNOS distribution in older AD mice caused by FUS raises the concern that our protocol may increase ischemia, while the increase in intra-neuronal eNOS may counteract that effect via protection of synaptic function. These findings also identify two candidate therapeutic windows for our FUS treatment protocol, each requiring more research before translation to humans. One window is early intervention to maximize Aβ plaque removal via activation of microglia. The second is later intervention to protect synaptic function if it is possible to mitigate the potential ischemic risk caused by the differential effects of FUS on eNOS.

A sensitivity analysis of two mesoscale models: COAMPS and WRF

Marzban, C., R. Tardif, and S. Sandgathe, "A sensitivity analysis of two mesoscale models: COAMPS and WRF," Mon. Wea. Rev., 148, 2997-3014, doi:10.1175/MWR-D-19-0271.1, 2020.

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6 Jul 2020

A sensitivity analysis methodology recently developed by the authors is applied to COAMPS and WRF. The method involves varying model parameters according to Latin Hypercube Sampling, and developing multivariate multiple regression models that map the model parameters to forecasts over a spatial domain. The regression coefficients and p values testing whether the coefficients are zero serve as measures of sensitivity of forecasts with respect to model parameters. Nine model parameters are selected from COAMPS and WRF, and their impact is examined on nine forecast quantities (water vapor, convective and gridscale precipitation, and air temperature and wind speed at three altitudes). Although the conclusions depend on the model parameters and specific forecast quantities, it is shown that sensitivity to model parameters is often accompanied by nontrivial spatial structure, which itself depends on the underlying forecast model (i.e., COAMPS vs WRF). One specific difference between these models is in their sensitivity with respect to a parameter that controls temperature increments in the Kain–Fritsch trigger function; whereas this parameter has a distinct spatial structure in COAMPS, that structure is completely absent in WRF. The differences between COAMPS and WRF also extend to the quality of the statistical models used to assess sensitivity; specifically, the differences are largest over the waters off the southeastern coast of the United States. The implication of these findings is twofold: not only is the spatial structure of sensitivities different between COAMPS and WRF, the underlying relationship between the model parameters and the forecasts is also different between the two models.

Sensitivity analysis of the spatial structure of forecasts in mesoscale models: Noncontinuous model parameters

Marzban, C., R. Tardif, and S. Sandgathe, "Sensitivity analysis of the spatial structure of forecasts in mesoscale models: Noncontinuous model parameters," Mon. Wea. Rev., 148, 1717-1735, doi:, 2020.

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1 Apr 2020

In a recent work, a sensitivity analysis methodology was described that allows for a visual display of forecast sensitivity, with respect to model parameters, across a gridded forecast field. In that approach, sensitivity was assessed with respect to model parameters that are continuous in nature. Here, the analogous methodology is developed for situations involving noncontinuous (discrete or categorical) model parameters. The method is variance based, and the variances are estimated via a random-effects model based on 2k–p fractional factorial designs and Graeco-Latin square designs. The development is guided by its application to model parameters in the stochastic kinetic energy backscatter scheme (SKEBS), which control perturbations at unresolved, subgrid scales. In addition to the SKEBS parameters, the effect of daily variability and replication (both, discrete factors) are also examined. The forecasts examined are for precipitation, temperature, and wind speed. In this particular application, it is found that the model parameters have a much weaker effect on the forecasts as compared to the effect of daily variability and replication, and that sensitivities, weak or strong, often have a distinctive spatial structure that reflects underlying topography and/or weather patterns. These findings caution against fine-tuning methods that disregard 1) sources of variability other than those due to model parameters, and 2) spatial structure in the forecasts.

More Publications

Acoustics Air-Sea Interaction & Remote Sensing Center for Industrial & Medical Ultrasound Electronic & Photonic Systems Environmental & Information Systems Ocean Engineering Ocean Physics Polar Science Center
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