A novel cognitive-motor exercise program delivered via a tablet to improve mobility in older people with cognitive impairment - StandingTall Cognition and Mobility.

BACKGROUND: Evidence-based interventions to improve mobility in older people include balance, strength and cognitive training. Digital technologies provide the opportunity to deliver tailored and progressive programs at home. However, it is unknown if they are effective in older people, especially in those with cognitive impairment. OBJECTIVE: The aim of this study was to examine the efficacy of a novel tablet-delivered cognitive-motor program on mobility in older people with cognitive impairment. METHODS: This was a 6-month single-blind randomised controlled trial of older people living in the community with subjective and/or objective cognitive impairment. Participants randomised to the intervention were asked to follow a 120 min per week balance, strength and cognitive training program delivered via an app on an iPad. Both the intervention and control group received monthly phone calls and health fact sheets. The primary outcome measure was gait speed. Secondary measures included dual-task gait speed, balance (step test, FISCIT-4), 5 sit to stand test, cognition (executive function, memory, attention), mood and balance confidence. Adherence, safety, usability and feedback were also measured. RESULTS: The planned sample size of 110 was not reached due to COVID-19 restrictions. A total of 93 (mean age 72.8 SD 7.0 years) participants were randomised to the two groups. Of these 77 participants returned to the follow-up clinic. In intention-to-treat analysis for gait speed, there was a non-significant improvement favouring the intervention group (ß 0.04 m/s 95% CI -0.01, 0.08). There were no significant findings for secondary outcomes. Adherence was excellent (84.5%), usability of the app high (76.7% SD 15.3) and no serious adverse events were reported. Feedback on the app was positive and included suggestions for future updates. CONCLUSION: Due to COVID-19 the trial was under powered to detect significant results. Despite this, there was a trend towards improvement in the primary outcome measure. The excellent adherence and positive feedback about the app suggest a fully powered trial is warranted.

Contrast-enhanced MRI-guided photodynamic cancer therapy with a pegylated bifunctional polymer conjugate.

PURPOSE: To study contrast-enhanced MRI guided photodynamic therapy with a pegylated bifunctional polymer conjugate containing an MRI contrast agent and a photosensitizer for minimally invasive image-guided cancer treatment. METHODS: Pegylated and non-pegylated poly-(L-glutamic acid) conjugates containing mesochlorin e6, a photosensitizer, and Gd(III)-DO3A, an MRI contrast agent, were synthesized. The effect of pegylation on the biodistribution and tumor targeting was non-invasively visualized in mice bearing MDA-MB-231 tumor xenografts with MRI. MRI-guided photodynamic therapy was carried out in the tumor bearing mice. Tumor response to photodynamic therapy was evaluated by dynamic contrast enhanced MRI and histological analysis. RESULTS: The pegylated conjugate had longer blood circulation, lower liver uptake and higher tumor accumulation than the non-pegylated conjugate as shown by MRI. Site-directed laser irradiation of tumors resulted in higher therapeutic efficacy for the pegylated conjugate than the non-pegylated conjugate. Moreover, animals treated with photodynamic therapy showed reduced vascular permeability on DCE-MRI and decreased microvessel density in histological analysis. CONCLUSIONS: Pegylation of the polymer bifunctional conjugates reduced non-specific liver uptake and increased tumor uptake, resulting in significant tumor contrast enhancement and high therapeutic efficacy. The pegylated poly(L-glutamic acid) bifunctional conjugate is promising for contrast enhanced MRI guided photodynamic therapy in cancer treatment.

Polymer platforms for drug delivery and biomedical imaging.

Biocompatible synthetic polymers have demonstrated advantageous pharmacokinetic properties as compared to small molecular agents. Incorporation of low molecular weight therapeutics and imaging agents into biocompatible polymers can optimize their pharmacokinetic properties with improved efficacy of therapy and diagnostic imaging, respectively. We have applied the concept of drug delivery to design safe and effective contrast agents for magnetic resonance imaging (MRI) and used biomedical imaging in non-invasive evaluation of drug delivery and image-guided therapy. We summarize here the recent progress in our research on biodegradable macromolecular MRI contrast agents, non-invasive visualization of in vivo drug delivery of polymeric conjugates with contrast enhanced MRI, and contrast enhanced MRI guided photodynamic therapy. The preliminary results have shown that biocompatible polymers can be used as an effective platform for drug delivery and biomedical imaging. Safe and effective imaging agents can be designed by using the concept of polymeric drug delivery. Biomedical imaging can be used as a non-invasive method for the evaluation of in vivo drug delivery of polymeric drug delivery systems. The combination of drug delivery and biomedical imaging can result in image-guided therapies, which include tumor detection, therapy and non-invasive evaluation of therapeutic responses.

Contrast-enhanced magnetic resonance angiography with biodegradable (Gd-DTPA)-cystamine copolymers: comparison with MS-325 in a swine model.

The purpose of this study is to evaluate the use of (Gd-DTPA)-cystamine copolymers (GDCC), a novel biodegradable intravascular polydisulfide-based macromolecular gadolinium(III) contrast agent, for first-pass and steady-state contrast-enhanced magnetic resonance angiography (MRA) in a swine model. A breath-hold background-suppressed 3D MRA of the thorax was performed for first-pass imaging and repeated every 10 min after GDCC injection to monitor the tissue enhancement time course. A navigator-gated 3D MRA of the coronary arteries was performed during steady state following the first-pass imaging. Imaging with intravascular agent MS-325 approximately 1 h after GDCC injection was also included for comparison. Experimental results indicated that GDCC provided significant blood signal-to-noise ratio (SNR) improvement, approximately 1633% for first-pass and 33% for steady-state contrast-enhanced MRA. Compared to MS-325, GDCC provided similar blood enhancement for first-pass and steady-state imaging but with a different tissue enhancement time course. The blood SNR enhancement half-time was 10 +/- 6 min for GDCC and 46 +/- 33 min for MS-325. GDCC provided less enhancement in the liver, bone growth plates, and muscle than MS-325.

Contrast enhanced MRI-guided photodynamic therapy for site-specific cancer treatment.

Photodynamic therapy (PDT) is a minimally invasive and effective approach for cancer treatment. It is potentially useful for treating tumors that are not accessible to surgery, radiation, or destructive ablations, and are resistant to chemotherapy. Efficacious treatment of interstitial tumors with PDT requires efficient delivery of photosensitizers and accurate location of tumor tissues for effective light irradiations. In this study we performed contrast-enhanced (CE) MRI-guided PDT with a bifunctional polymer conjugate containing both a magnetic resonance imaging (MRI) contrast agent and a photosensitizer, poly(L-glutamic acid) (PGA)-(Gd-DO3A)-mesochlorin e(6) (Mce(6)). The efficacy of the bifunctional conjugate in cancer CE-MRI and cancer treatment was evaluated in athymic nude mice bearing MDA-MB-231 human breast carcinoma xenografts, with PGA-(Gd-DO3A) used as a control. The polymer conjugates preferentially accumulated in the solid tumor due to the hyperpermeability of the tumor vasculature, resulting in significant tumor enhancement for accurate tumor detection and localization by MRI. Significant therapeutic response was observed for PDT with the bifunctional conjugate as compared to the control. CE-MRI-guided PDT with the bifunctional conjugate is effective for tumor detection and minimally invasive cancer treatment.