Factors associated with pain intensity and analgesic use during inpatient rehabilitation for hip fracture.

PURPOSE: Effective pain management is vital for hip fracture recovery, yet the factors influencing pain reporting and pain medication use during inpatient rehabilitation for hip fractures are not well understood. This observational study aimed to (a) determine how cognitive abilities, expressive and receptive language abilities, and age are related to average daily pain intensity and analgesic use and (b) how average daily pain intensity and analgesic use are related to length of stay and functional outcomes in rehabilitation. DESIGN: Data were retrospectively obtained from 163 patients recovering from unilateral trochanteric fractures of the femur. RESULTS: During the first week of rehabilitation, patients received a daily average of 1,147.8 ± 978 mg of acetaminophen and a morphine milligram equivalent of 15.3 ± 18.2. Multivariable regression revealed independent relationships between more intact general cognitive abilities (B = -0.40, 95% CI [-0.70, -0.11]), and older age (B = -0.41, 95% CI [-0.70, -0.11]) with lower average daily pain intensity. Higher average daily pain intensity (B = 0.97, 95% CI [0.75, 1.20]) was independently related to greater opioid use. The length of stay was shorter among patients administered higher daily doses of acetaminophen (B = 0.03, 95% CI [-0.05, -0.01]). Average daily pain intensity and analgesic use were not related to functional outcomes in multivariable models. CONCLUSIONS: These findings inform the considerations for assessing and treating pain during inpatient rehabilitation. Supplemental strategies for assessing pain in older patients and alternative pain mitigation strategies for patients with impaired cognitive abilities should be considered. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessing Clinically Important Differences During Rehabilitation for Stroke: A Pilot Study Evaluating Anchor and Distribution Derived Estimates of Physical Function Change in Classically Summed and Rasch Models of Section GG of the Inpatient Rehabilitation Facility Patient Assessment Instrument.

OBJECTIVE: To determine clinically important differences (CIDs) on Section GG physical functioning scores on the Centers for Medicare and Medicaid Services (CMS) Inpatient Rehabilitation Facility Assessment Instrument (IRF-PAI) for patients with stroke, using anchor and distribution-based approaches. DESIGN: Pilot prospective observational cohort study. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: Patients with stroke (N=208). INTERVENTIONS: Physicians assessed improvements during rehabilitation using the modified Rankin scale (mRS). Improvements (≥1 point) on the mRS were used as the anchor for establishing CIDs. MAIN OUTCOME MEASURES: Classically summed and Rasch transformed Section GG change scores associated with clinically important improvements on the mRS. RESULTS: A total of 166 patients (79.8%) improved ≥1 point on the mRS. Change scores of 27, 9, and 16 on Section GG total physical functioning (self-care + mobility), self-care, and mobility/walk scales, respectively, had high sensitivity (0.82-0.85) but low specificity (0.52-0.69) in identifying patients improving on the mRS. Positive predictive values ranged from 0.87 to 0.91, and negative predictive values ranged from 0.42 to 0.52. Total physical functioning and selfcare anchor-derived change scores were similar to the reliable change index (RCI [2.77 × SEM]), calculated as 28 and 10 points, respectively, whereas anchor-derived mobility/walk scale change scores were equivalent to 1.96 × SEM. Exploratory Rasch modeling identified 3 Section GG subscales (R-Self-Care, R-Mobility, and R-Walking). Improvements on the R-Walking subscale were most correlated with mRS improvements (ρ=-0.47); however, accuracy of CID estimates was not improved. CONCLUSIONS: Cut-off scores obtained using the mRS anchor aligned with more robust estimates of change, as estimated by distribution-based measures. While patients achieving anchor-derived cut-offs have a high probability of mRS improvement, change scores may fail to detect clinically meaningful improvements at these same thresholds. Alternative criteria for determining MCID/CIDs, should be explored. Rasch models require further validation.

Concurrent Validation of the Inpatient Rehabilitation Facility Patient Assessment Instrument Version 1.4; Sections GG, B, and C.

OBJECTIVE: To validate Sections GG (Self-Care and Mobility Assessment), B (Hearing, Speech, and Vision), and C (Cognitive Patterns) of the Centers for Medicare and Medicaid Services Inpatient Rehabilitation Facility Patient Assessment Instrument (CMS-IRF PAI) Version 1.4 in comparison with Functional Independence Measure (FIM) motor subscale (FIMm) and cognitive subscale (FIMc). DESIGN: Retrospective cohort. SETTING: Single inpatient rehabilitation facility. PARTICIPANTS: Cohort of 1296 patients admitted for rehabilitation after stroke, between October 1, 2016, and October 1, 2019. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sections GG, B, and C scores were compared with FIMm and FIMc using Spearman's and Bland-Altman Analyses. RESULTS: Sections GG and FIMm were highly correlated on admission (ρ=0.919, P<.001) and discharge (ρ=0.929, P<.001). Ceiling effects at discharge were more pronounced for Section GG (8.6%). Bland-Altman analyses revealed a bias toward higher scores on Section GG vs FIMm on admission (Bias=2.3%, P<.001), and discharge (Bias=6.2%, P<.001). Section GG showed bias toward greater gains in function (Bias=3.9%, P<.001), particularly in walking and stairs (bias=3.71%, P<.001). Comparable self-care items accounted for a smaller percentage of the Section GG gains compared with FIMm (bias=-7.5%, P<.001). The internal validity of a scale consisting of Section B and C (B+C scale) was good, (Cronbach's alpha=0.868) and was highly correlated with FIMc (ρ=0.745), but rated patients at a higher level of cognition (bias=20.0%, P<.001) and had a greater ceiling effect (20.4%) on admission compared with the FIMc (0.6%). CONCLUSION: The B+C scale and Section GG were correlated with FIMc and FIMm subscales but biased toward higher ratings of ability. Ceiling effects may limit discrimination at higher level of cognition/functional independence. The clinical acceptability of Section GG total scores as an outcome measure and predictor of long-term outcomes requires further study.

Predicting Falls in Rehabilitation: A Comparison of Three Instruments Including Hester Davis.

PURPOSE: The aim of this study was to evaluate the ability of the Hester Davis Scale (HDS), Section GG, and facility fall risk assessment scores to predict patients who fall during inpatient rehabilitation. DESIGN: This study was an observational quality improvement project. METHODS: Nurses administered the HDS in parallel to the facility's current fall risk assessment and Section GG of the Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility Patient Assessment Instrument. Receiver operating characteristic curves were compared in 1,645 patients. Relationships of individual scale items to falls were also assessed. RESULTS: The HDS (area under the curve [AUC] = .680, 95% CI [.626, .734]), facility fall risk assessment (AUC = .688, 95% CI [.637, .740]), and Section GG scores (AUC = .687, 95% CI [.638, .735]) adequately identified patients who fell. AUCs did not significantly differ between assessments. HDS scores of ≥13, facility scores of ≥14, and Section GG scores of ≤51 resulted in the highest sensitivity/specificity balance. CONCLUSIONS: HDS, facility fall risk assessment, and Section GG scores adequately and similarly identified patients of mixed diagnoses at risk of falling in inpatient rehabilitation. CLINICAL RELEVANCE TO THE PRACTICE OF REHABILITATION NURSING: Rehabilitation nurses have several options including the HDS and Section GG to identify patients at greatest risk of falling.

Characteristics and Outcomes of COVID-19 Survivors Requiring Inpatient Rehabilitation: A Comparison of Two Waves.

OBJECTIVE: Many survivors of severe or critical COVID-19 have required rehabilitation during the pandemic. The primary objective was to compare characteristics and outcomes of survivors of severe or critical COVID-19 admitted to the inpatient rehabilitation facility during the first two waves of the pandemic. Our secondary objective was to identify the factors contributing to functional dependence on admission, discharge, and length of stay. DESIGN: This is a retrospective cohort study of 138 patients admitted to an inpatient rehabilitation facility in two waves after hospitalization for severe or critical COVID-19 illness between April 1, 2020, and May 3, 2021. RESULTS: Inpatient rehabilitation facility patients in wave 2 had significantly greater functional independence (GG scores) on admission (52; interquartile range, 44-58 vs 41; interquartile range, 28-52), lower incidence of dysphagia and anemia. The patients in both waves experienced similar functional improvement efficiencies with a median GG score change of 3.6 per day and similar discharge GG scores. Neurological sequela (odds ratio, 0.12; P < 0.001) and anemia (odds ratio, 1.35; P < 0.002) were identified as independent predictors of functional independence on admission. CONCLUSIONS: Patients with functional deficits after COVID-19 should be considered for acute inpatient rehabilitation as both patient cohorts benefited from their inpatient rehabilitation facility stays with similar length of stays (11-12 days) and discharge to home rates (88%-90%).

Comparison of the Brief Interview for Mental Status (BIMS) and Montreal Cognitive Assessment (MoCA) for identifying cognitive impairments and predicting rehabilitation outcomes in an inpatient rehabilitation facility.

BACKGROUND: The Brief Interview for Mental Status (BIMS) is the Centers for Medicare and Medicaid Services' primary cognitive assessment for multiple health care settings. However, research suggests that the BIMS has low sensitivity in detecting mild cognitive impairment in community samples and nursing home residents. OBJECTIVE: To determine the sensitivity of the BIMS in identifying patients with mild or moderate cognitive impairments in an inpatient rehabilitation setting and the relationship of BIMS and Montreal Cognitive Assessment (MoCA) scores with rehabilitation outcomes. DESIGN: Retrospective cohort. SETTING: Inpatient rehabilitation facility. PATIENTS: A total of 2252 patients admitted for orthopedic or general rehabilitation. METHODS: The sensitivity and specificity of the BIMS for identification of cognitive impairments were determined using validated cutoff scores on the MoCA as criterion. Multivariable ordinal regression was employed to determine if MoCA and BIMS scores were independent predictors of rehabilitation outcomes. MAIN OUTCOME MEASUREMENTS: Functional independence at discharge (GG scores), rehabilitation efficiency (GG change per day), length of stay (LOS), and discharge destination. RESULTS: The BIMS had low sensitivity in identifying moderate (0.384) or mild (0.257) cognitive impairment. Patients classified as having moderate cognitive impairment on the MoCA had lower GG scores at discharge (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.30 to 0.46) and rehabilitation efficiency (OR 0.43, CI 0.34 to 0.53) compared to individuals identified as impaired on the BIMS (GG scores: OR 0.63, CI 0.52 to 0.78; efficiency: OR 0.71, CI 0.58 to 0.86). LOS (OR 1.49, CI 1.19 to 1.85) and discharge destination (OR 0.47, CI 0.28 to 0.77) were uniquely predicted in patients identified as moderately impaired on the MoCA but not the BIMS (LOS: OR 0.99, CI 0.80 to 1.21; discharge home: OR 0.93, CI 0.62 to 1.38). CONCLUSIONS: The BIMS had low sensitivity for detection of mild and moderate cognitive impairments. Compared to the MoCA, the BIMS was less effective at predicting rehabilitation outcomes.

Prism Adaptation Treatment of Spatial Neglect: Feasibility During Inpatient Rehabilitation and Identification of Patients Most Likely to Benefit.

Objective: Spatial Neglect is prevalent among stroke survivors, yet few treatments have evidence supporting efficacy. This study examines the feasibility of Prism Adaptation Treatment (PAT) within an inpatient rehabilitation facility and the degree by which PAT improves symptoms of spatial neglect and functional independence among sub-acute survivors of right hemispheric stroke. Design: In this retrospective cohort study, 37 right hemispheric stroke patients were identified as having received at least 4 PAT sessions during their inpatient stay. Spatial neglect and functional independence levels of patients in the PAT cohort were compared to a matched active control group comprised of rehabilitation patients receiving alternative therapies to address neglect admitted during the same time period. Results: Most patients received the full recommended 10 sessions of PAT (average sessions completed = 8.6). A higher percentage of severe neglect patients receiving PAT (69%) displayed clinically significant gains on FIM (≥22 points) compared to those receiving alternative treatments (6%). Patients with mild or moderate neglect in the PAT cohort did not exhibit greater benefit than controls. Conclusion: Provision of PAT for treatment of spatial neglect in right hemispheric stroke patients was feasible during the inpatient rehabilitation admission. Patients with severe neglect showed the most benefit from PAT. Clinical Trial Registration: This study was registered as a retrospective observational study on Itab Clinical Trials.gov. NCT04977219.

Functional outcomes and post-discharge care sought by patients with COVID-19 compared to matched controls after completing inpatient acute rehabilitation.

INTRODUCTION: A subset of patients with coronavirus disease 19 (COVID-19) can develop severe illness, resulting in significant functional and cognitive deficits that require acute inpatient rehabilitation. Guidelines following discharge from acute inpatient rehabilitation have not yet been established. This study seeks to establish outcomes of rehabilitation patients with COVID-19 and characterize their need for long-term care. OBJECTIVE: To determine the functional outcomes and utilization of follow-up medical care for patients with COVID-19 90 days following discharge from acute inpatient rehabilitation, as compared to rehabilitation impairment and age-matched controls. DESIGN: Prospective, single-center cohort study. SETTING: Inpatient rehabilitation facility (IRF). PATIENTS: Sixty-four patients recovering from COVID-19 and 64 age and impairment group category controls were identified to answer survey questions following discharge from inpatient rehabilitation. A total of 36 patients participated in the study (18 patients with COVID-19 and 18 controls). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Functional outcomes at discharge (GG Self-Care and Mobility Activities items of the IRF-PAI Version 3.0), hospital readmissions, and follow-up care sought by patients. RESULTS: The COVID-19 patient group had similar improvements in functional outcomes as compared to controls. Patients with COVID-19 required fewer 0-90 day readmissions than their matched controls (22.2% vs 61.1%, P < .05), but there were no differences in 0-90 day urgent care/emergency department visits, clinic visits and use of outpatient therapies. CONCLUSIONS: Patients with functional deficits as a result of COVID-19 who require multiple therapy disciplines should be considered for acute inpatient rehabilitation as this study demonstrates their ability to participate in and benefit from IRF level care.

How We Assess Spatial Neglect Matters: Prevalence of Spatial Neglect as Measured by the Catherine Bergego Scale and Impact on Rehabilitation Outcomes.

OBJECTIVE: The aim of this study was to determine the prevalence and functional impact of unilateral spatial neglect on right hemisphere stroke patients in an inpatient rehabilitation facility using a multidimensional, functionally based behavioral measure (Catherine Bergego Scale [CBS]). DESIGN: This was a retrospective cohort study of 742 consecutive admissions of patients with right hemispheric stroke to an inpatient rehabilitation facility. Spatial neglect was assessed using the CBS. Functional impact of neglect was measured by hospital length of stay, Functional Independence Measure change per day, discharge destination, and number of falls. RESULTS: As measured by the CBS, 86% of the right hemisphere stroke patients had symptoms of spatial neglect. Moderate and severe neglect was associated with less Functional Independence Measure change per day and lower rates of community discharge. The presence of neglect was not significantly associated with fall rate or length of hospital stay after controlling for admission Functional Independence Measure scores and age. The "difficulty looking left" CBS item had the strongest relationship with total CBS scores and effectively predicted Functional Independence Measure change per day and discharge destination. CONCLUSIONS: Using a sensitive measure, the CBS, rates of spatial neglect are extremely high in right hemisphere stroke patients entering inpatient rehabilitation. Both identification and determination of neglect severity are extremely important given their significant relationship to rehabilitation outcomes and discharge destinations. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) describe why carefully assessing spatial neglect in right hemisphere stroke patients is important; (2) identify multiple dimensions of spatial neglect assessed by the Catherine Bergego Scale and how this approach differs from traditional paper and pencil assessment methods; and (3) describe the relationship between spatial neglect as measured by the Catherine Bergego Scale and functional outcomes of right hemisphere stroke patients in inpatient rehabilitation settings. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The effect of engineered nanotopography of electrospun microfibers on fiber rigidity and macrophage cytokine production.

Currently, it is unknown how the mechanical properties of electrospun fibers, and the presentation of surface nanotopography influence macrophage gene expression and protein production. By further elucidating how specific fiber properties (mechanical properties or surface properties) alter macrophage behavior, it may be possible to create electrospun fiber scaffolds capable of initiating unique cellular and tissue responses. In this study, we determined the elastic modulus and rigidity of fibers with varying topographies created by finely controlling humidity and including a non-solvent during electrospinning. In total,five fiber scaffold types were produced. Analysis of fiber physical properties demonstrated no change in fiber diameter amongst the five different fiber groups. However, the four different fibrous scaffolds with nanopits or divots each possessed different numbers of pits with different nanoscale dimensions. Unpolarized bone marrow derived murine macrophages (M0), macrophages polarized towards a pro-inflammatory phenotype (M1), or macrophages polarized towards anti-inflammatory phenotype (M2b) were placed onto each of the scaffolds and cytokine RNA expression and protein production were analyzed. Specific nanotopographies did not appreciably alter cytokine production from undifferentiated macrophages (M0) or anti-inflammatory macrophages (M2b), but a specific fiber (with many small pits) did increase IL-12 transcript and IL-12 protein production compared to fibers with small divots. When analyzing the mechanical properties between fibers with divots or with many small pits,divoted fibers possessed similar elastic moduli but different stiffness values. In total,we present techniques capable of creating unique electrospun fibers. These unique fibers have varying fiber mechanical characteristics and modestly modulate macrophage cytokine expression.

Reduced Atherosclerosis in apoE-inhibitory FcγRIIb-Deficient Mice Is Associated With Increased Anti-Inflammatory Responses by T Cells and Macrophages.

OBJECTIVE: Fcγ receptors (FcγRs) are classified as activating (FcγRI, III, and IV) and inhibitory (FcγRII) receptors. We have reported that deletion of activating FcγRs in apolipoprotein E (apoE) single knockout mice attenuated atherosclerosis. In this report, we investigated the hypothesis that deficiency of inhibitory FcγRIIb exacerbates atherosclerosis. APPROACH AND RESULTS: ApoE-FcγRIIb double knockout mice, congenic to the C57BL/6 (apoE-FcγRIIbB6 (-/-)), were generated and atherosclerotic lesions were assessed. In contrary to our hypothesis, when compared with apoE single knockout mice, arterial lesions were significantly decreased in apoE-FcγRIIbB6 (-/-) male and female mice fed chow or high-fat diets. Chimeric mice generated by transplanting apoE-FcγRIIbB6 (-/-) marrow into apoE single knockout mice also developed reduced lesions. CD4(+) T cells from apoE-FcγRIIbB6 (-/-) mice produced higher levels of interleukin-10 and transforming growth factor-ß than their apoE single knockout counterparts. As our findings conflict with a previous report using apoE-FcγRIIb129/B6 (-/-) mice on a mixed genetic background, we investigated whether strain differences contributed to the anti-inflammatory response. Macrophages from FcγRIIb129/B6 (-/-) mice on a mixed genetic background produced more interleukin-1ß and MCP-1 (monocyte chemoattractant protein-1) in response to immune complexes, whereas congenic FcγRIIbB6 (-/-) mice generated more interleukin-10 and significantly less interleukin-1ß. Interestingly, the expression of lupus-associated slam genes, located in proximity to fcgr2b in mouse chromosome 1, is upregulated only in mixed FcγRIIb129/B6 (-/-) mice. CONCLUSIONS: Our findings demonstrate a detrimental role for FcγRIIb signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-FcγRIIbB6 (-/-) mice. As 129/sv genome-derived lupus-associated genes have been implicated in lupus phenotype in FcγRIIb129/B6 (-/-) mice, our findings suggest possible epistatic mechanism contributing to the decreased lesions.

Anti-inflammatory immune skewing is atheroprotective: Apoe−/−FcγRIIb−/− mice develop fibrous carotid plaques.

BACKGROUND: Stroke, caused by carotid plaque rupture, is a major cause of death in the United States. Whereas vulnerable human plaques have higher Fc receptor (FcγR) expression than their stable counterparts, how FcγR expression impacts plaque histology is unknown. We investigated the role of FcγRIIb in carotid plaque development and stability in apolipoprotein (Apo)e−/− and Apoe−/−FcγRIIb−/− double knockout (DKO) animals. METHODS AND RESULTS: Plaques were induced by implantation of a shear stress­modifying cast around the carotid artery. Plaque length and stenosis were followed longitudinally using ultrasound biomicroscopy. Immune status was determined by flow cytometry, cytokine release, immunoglobulin G concentration and analysis of macrophage polarization both in plaques and in vitro. Surprisingly, DKO animals had lower plaque burden in both carotid artery and descending aorta. Plaques from Apoe−/− mice were foam­cell rich and resembled vulnerable human specimens, whereas those from DKO mice were fibrous and histologically stable. Plaques from DKO animals expressed higher arginase 1 (Arg­1) and lower inducible nitric oxide synthase (iNOS), indicating the presence of M2 macrophages. Analysis of blood and cervical lymph nodes revealed higher interleukin (IL)­10, immune complexes, and regulatory T cells (Tregs) and lower IL­12, IL­1ß, and tumor necrosis factor alpha (TNF­α) in DKO mice. Similarly, in vitro stimulation produced higher IL­10 and Arg­1 and lower iNOS, IL­1ß, and TNF­α in DKO versus Apoe−/− macrophages. These results define a systemic anti­inflammatory phenotype. CONCLUSIONS: We hypothesized that removal of FcγRIIb would exacerbate atherosclerosis and generate unstable plaques. However, we found that deletion of FcγRIIb on a congenic C57BL/6 background induces an anti­inflammatory Treg/M2 polarization that is atheroprotective.

The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions.

BACKGROUND: Missense mutations in AHI1 result in the neurodevelopmental ciliopathy called Joubert syndrome. RESULTS: Mutations in AHI1 decrease cilia formation, alter its localization and stability, and change its binding to HAP1 and NPHP1. CONCLUSION: Mutations in AHI1 affect ciliogenesis, AHI1 protein localization, and AHI1-protein interactions. SIGNIFICANCE: This study begins to describe how missense mutations in AHI1 can cause Joubert syndrome. Mutations in AHI1 cause Joubert syndrome (JBTS), a neurodevelopmental ciliopathy, characterized by midbrain-hindbrain malformations and motor/cognitive deficits. Here, we show that primary cilia (PC) formation is decreased in fibroblasts from individuals with JBTS and AHI1 mutations. Most missense mutations in AHI1, causing JBTS, occur in known protein domains, however, a common V443D mutation in AHI1 is found in a region with no known protein motifs. We show that cells transfected with AHI1-V443D, or a new JBTS-causing mutation, AHI1-R351L, have aberrant localization of AHI1 at the basal bodies of PC and at cell-cell junctions, likely through decreased binding of mutant AHI1 to NPHP1 (another JBTS-causing protein). The AHI1-V443D mutation causes decreased AHI1 stability because there is a 50% reduction in AHI1-V443D protein levels compared with wild type AHI1. Huntingtin-associated protein-1 (Hap1) is a regulatory protein that binds Ahi1, and Hap1 knock-out mice have been reported to have JBTS-like phenotypes, suggesting a role for Hap1 in ciliogenesis. Fibroblasts and neurons with Hap1 deficiency form PC with normal growth factor-induced ciliary signaling, indicating that the Hap1 JBTS phenotype is likely not through effects at PC. These results also suggest that the binding of Ahi1 and Hap1 may not be critical for ciliary function. However, we show that HAP1 has decreased binding to AHI1-V443D indicating that this altered binding could be responsible for the JBTS-like phenotype through an unknown pathway. Thus, these JBTS-associated missense mutations alter their subcellular distribution and protein interactions, compromising functions of AHI1 in cell polarity and cilium-mediated signaling, thereby contributing to JBTS.

Ultrasound biomicroscopy for longitudinal studies of carotid plaque development in mice: validation with histological endpoints.

Atherosclerosis is responsible for the death of thousands of Americans each year. The carotid constriction model of plaque development has recently been presented as a model for unstable plaque formation in mice. In this study we 1) validate ultrasound biomicroscopy (UBM) for the determination of carotid plaque size, percent stenosis, and plaque development in live animals, 2) determine the sensitivity of UBM in detecting changes in blood flow induced by carotid constriction and 3) test whether plaque formation can be predicted from blood flow parameters measured by UBM. Carotid plaques were induced by surgical constriction in Apo E⁻/⁻ mice. Arteries were imaged bi-weekly by UBM, at which time PW-Doppler measurements of proximal blood flow, as well as plaque length and percent stenosis were determined. Histology was performed 9 weeks post surgery. When compared to whole mount post-mortem measurements, UBM accurately reported carotid plaque length. Percent stenosis, based on transverse B-mode UBM measurements, correlated well with that calculated from histological sections. PW-Doppler revealed that constriction reduced maximum systolic velocity (v(max)) and duration of the systolic velocity peak (t(s)/t(t)). Pre-plaque (2 week post-surgery) PW-Doppler parameters (v(max) and t(s)/t(t)) were correlated with plaque length at 9 weeks, and were predictive of plaque formation. Correlation of initiating PW-Doppler parameters (v(max) and t(s)/t(t)) with resulting plaque length established the degree of flow disturbance required for subsequent plaque development and demonstrated its power for predicting plaque development.