Digital Graphic Follow-up Tool (Rehabkompassen) for Identifying Rehabilitation Needs Among People After Stroke: Randomized Clinical Feasibility Study.

BACKGROUND: Stroke is a leading cause of disability among adults, with heavy social and economic burden worldwide. A cost-effective solution is urgently needed to facilitate the identification of individual rehabilitation needs and thereby provide tailored rehabilitations to reduce disability among people who have had a stroke. A novel digital graphic follow-up tool Rehabkompassen has recently been developed to facilitate capturing the multidimensional rehabilitation needs of people who have had a stroke. OBJECTIVE: The aim of this study was to evaluate the feasibility and acceptability of conducting a definitive trial to evaluate Rehabkompassen as a digital follow-up tool among people who have had a stroke in outpatient clinical settings. METHODS: This pilot study of Rehabkompassen was a parallel, open-label, 2-arm prospective, proof-of-concept randomized controlled trial (RCT) with an allocation ratio of 1:1 in a single outpatient clinic. Patients who have had a stroke within the 3 previous months, aged ≥18 years, and living in the community were included. The trial compared usual outpatient visits with Rehabkompassen (intervention group) and without Rehabkompassen (control group) at the 3-month follow-up as well as usual outpatient visit with Rehabkompassen at the 12-month follow-up. Information on the recruitment rate, delivery, and uptake of Rehabkompassen; assessment and outcome measures completion rates; the frequency of withdrawals; the loss of follow-up; and satisfaction scores were obtained. The key outcomes were evaluated in both groups. RESULTS: In total, 28 patients (14 control, 14 Rehabkompassen) participated in this study, with 100 patients screened. The overall recruitment rate was 28% (28/100). Retention in the trial was 86% (24/28) at the 12-month follow-up. All participants used the tool as planned during their follow-ups, which provided a 100% (24/24) task completion rate of using Rehabkompassen and suggested excellent feasibility. Both patient- and physician-participants reported satisfaction with the instrument (19/24, 79% and 2/2, 100%, respectively). In all, 2 (N=2, 100%) physicians and 18 (N=24, 75%) patients were willing to use the tool in the future. Furthermore, modified Rankin Scale as the primary outcome and various stroke impacts as secondary outcomes were both successfully collected and compared in this study. CONCLUSIONS: This study demonstrated the high feasibility and adherence of the study protocol as well as the high acceptability of Rehabkompassen among patients who have had a stroke and physicians in an outpatient setting in comparison to the predefined criterion. The information collected in this feasibility study combined with the amendments of the study protocol may improve the future definitive RCT. The results of this trial support the feasibility and acceptability of conducting a large definitive RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915027; https://clinicaltrials.gov/ct2/show/NCT04915027.

Assessments of a novel digital follow-up tool Rehabkompassen® to identify rehabilitation needs among stroke patients in an outpatient setting.

Introduction: It remains a huge challenge to identify individual rehabilitation needs in a time-efficient manner for providing patient-tailored rehabilitation during the continuum of stroke care. We have recently demonstrated the usefulness of a paper-version Rehab-Compass as a follow-up tool. The aim of the current study was to develop a digital version of the Rehab-Compass and evaluate its usability and feasibility. Methods: The novel digital tool Rehabkompassen® was developed by an iterative and participatory design process. Patients' rehabilitation needs were visualized by the tool and used before, during, and after the consultation. The usability and feasibility of the tool was assessed by task completion rate, the System Usability Scale, and satisfaction questionnaires among 2 physicians and 24 adult stroke patients in an outpatient clinical setting. Results: Rehabkompassen® identified and graphically visualized a panoramic view of the stroke patients' multidimensional needs in individual- and group levels. The instrument appeared to be feasible and time efficient in clinical use with a 100% overall task completion rate for both patients and physicians. A majority of the patients reported that it was very easy or fairly easy to answer the digital questionnaires and to understand their own digital Rehab-Compass graph. Two physicians reported a high mean score on the System Usability Scale (95/100) and were positive about using the tool in the future. Conclusions: The current results indicated that Rehabkompassen® was a feasible, useful, and time-saving follow-up tool for the identification of rehabilitation needs among stroke survivors in the post-acute continuum of care after stroke. Further research is needed to evaluate the efficacy of the digital instrument among stroke patients.

A tactile resonance sensor for prostate cancer detection - evaluation on human prostate tissue.

Prostate cancer surgery risks erectile problems and incontinence for the patient. An instrument for guiding surgeons to avoid nerve bundle damage and ensure complete cancer removal is desirable. We present a tactile resonance sensor made of PZT ceramics, mounted in a 3D motorized translation stage for scanning and measuring tissue stiffness for detecting cancer in human prostate. The sensor may be used during surgery for guidance, scanning the prostate surface for the presence of cancer, indicating migration of cancer cells into surrounding tissue. Ten fresh prostates, obtained from patients undergoing prostate cancer surgery, were cut into 0.5 cm thick slices. Each slice was measured for tissue stiffness at about 25 different sites and compared to histology for validation cancer prediction by stiffness. The statistical analysis was based on a total of 148 sites with non-cancer and 40 sites with cancer. Using a generalized linear mixed model (GLMM), the stiffness data predicted cancer with an area under the curve of 0.74, after correcting for overfitting using bootstrap validation. Mean prostate stiffness on the logarithmic scale (p = 0.015) and standardized Z-scores (p = 0.025) were both significant predictors of cancer. This study concludes that stiffness measured by the tactile resonance sensor is a significant predictor of prostate cancer with potential for future development towards a clinical instrument for surgical guidance.

Prostate Cancer Detection with a Tactile Resonance Sensor-Measurement Considerations and Clinical Setup.

Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (p < 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.

Sensitivity improvements of a resonance-based tactile sensor.

Resonance-based contact-impedance measurement refers to the application of resonance sensors based on the measurement of the changes in the resonance curve of an ultrasonic resonator in contact with a surface. The advantage of the resonance sensor is that it is very sensitive to small changes in the contact impedance. A sensitive micro tactile sensor (MTS) was developed, which measured the elasticity of soft living tissues at the single-cell level. In the present paper, we studied the method of improving the touch and stiffness sensitivity of the MTS. First, the dependence of touch sensitivity in relation to the resonator length was studied by calculating the sensitivity coefficient at each length ranging from 9 to 40 mm. The highest touch sensitivity was obtained with a 30-mm-long glass needle driven at a resonance frequency of 100 kHz. Next, the numerical calculation of contact impedance showed that the highest stiffness sensitivity was achieved when the driving frequency was 100 kHz and the contact-tip diameter of the MTS was 10 µm. The theoretical model was then confirmed experimentally using a phase-locked-loop-based digital feedback oscillation circuit. It was found that the developed MTS, whose resonant frequency was 97.030 kHz, performed with the highest sensitivity of 53.2 × 106 Hz/N at the driving frequency of 97.986 kHz, i.e. the highest sensitivity was achieved at 956 Hz above the resonant frequency.

A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy- first investigations of single biological cells.

The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.

Indentation loading response of a resonance sensor--discriminating prostate cancer and normal tissue.

Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

Optical fibre probe NIR Raman measurements in ambient light and in combination with a tactile resonance sensor for possible cancer detection.

First measurements on a combined instrument with a thin fibre optic Raman probe mounted inside a hollow tactile resonance sensor have been performed in ambient light on porcine tissue. The ambient fluorescent light was removed successfully from the spectra. The stiffness and the biomolecular composition of the tissue were analysed.

Contact angle and indentation velocity dependency for a resonance sensor--evaluation on soft tissue silicone models.

Human tissue stiffness can vary due to different tissue conditions such as cancer tumours. Earlier studies show that stiffness may be detected with a resonance sensor that measures frequency shift and contact force at application. Through the frequency shift and the contact force, a tissue stiffness parameter can be derived. This study evaluated how the probe application angle and indentation velocity affected the results and determined the maximum parameter errors. The evaluation was made on flat silicone discs with specified hardness. The frequency shift, the force and the stiffness parameter all varied with contact angle and indentation velocity. A contact angle of ≤10° was acceptable for reliable measurements. A low indentation velocity was recommended. The maximum errors for the system were <1.1% of the measured values. It was concluded that contact angle and indentation velocity have to be considered in the clinical setting. The angular dependency is especially important in clinical use for studying stiffness of human soft tissue, e.g. in prostate cancer diagnosis.

A FEM-based method using harmonic overtones to determine the effective elastic, dielectric, and piezoelectric parameters of freely vibrating thick piezoelectric disks.

To gain an understanding of the electroelastic properties of tactile piezoelectric sensors used in the characterization of soft tissue, the frequency-dependent electric impedance response of thick piezoelectric disks has been calculated using finite element modeling. To fit the calculated to the measured response, a new method was developed using harmonic overtones for tuning of the calculated effective elastic, piezoelectric, and dielectric parameters. To validate the results, the impedance responses of 10 piezoelectric disks with diameter-to-thickness ratios of 20, 6, and 2 have been measured from 10 kHz to 5 MHz. A two-dimensional, general purpose finite element partial differential equation solver with adaptive meshing capability run in the frequency-stepped mode, was used. The equations and boundary conditions used by the solver are presented. Calculated and measured impedance responses are presented, and resonance frequencies have been compared in detail. The comparison shows excellent agreement, with average relative differences in frequency of 0.27%, 0.19%, and 0.54% for the samples with diameter-to-thickness ratios of 20, 6, and 2, respectively. The method of tuning the effective elastic, piezoelectric, and dielectric parameters is an important step toward a finite element model that describes the properties of tactile sensors in detail.

Effects of snap-freezing and near-infrared laser illumination on porcine prostate tissue as measured by Raman spectroscopy.

Most Raman spectroscopic studies on tissue are performed in vitro. To assure that the results are applicable to in vivo examinations, preparation protocols and measurement procedures of tissue for in vitro studies should preserve tissue characteristics close to the native state. This study had two aims. The first was to elucidate if photoinduced effects arise during 5 minutes' continuous illumination of tissue with an 830 nm laser at an irradiance of approximately 3 x 10(10) W/m2. The second was to investigate the effects of snap-freezing of porcine prostate tissue in liquid nitrogen and subsequent storage at -80 degrees C, by means of multivariate analysis. 830 nm laser illumination of the specified irradiance did not affect the Raman spectra. A decrease of the spectral background was observed, likely due to photobleaching of tissue fluorophores. Snap-freezing and subsequent storage at -80 degrees C gave rise to subtle but significant alterations in Raman spectra, most likely related to changes in the protein conformations.

Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1)F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Spatial variations in prostate tissue histology as measured by a tactile resonance sensor.

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensor's stiffness-measuring properties can reflect tissue pathology. The change in the frequency of the resonating system and the change in force when contact is made with tissue are used as a stiffness parameter. Earlier stiffness measurements of prostate tissue in vitro demonstrate variations related to tissue composition. In this study, measured stiffness from two human prostate specimens was compared to histological composition of prostate tissue below and around the measurement points. Tissue stiffness was measured with the resonance sensor system. Tissue composition was measured at four different depths in the tissue specimen using a microscopic-image-based morphometrical method. With this method, the proportion of tissue types was determined at the points of intersections in a circular grid on the images representing each measurement point. Numerical values were used for weighting the tissue proportions at different depths in the tissue specimen. For an impression depth of 1.0 mm, the sensing depth in this study was estimated to be 3.5-5.5 mm. Stiffness variations due to horizontal tissue variations were investigated by studying the dependence of the size of the circular grid area relative to the contact area of the sensor tip. The sensing area (grid radius) was estimated to be larger than the contact area (contact radius) between the sensor tip and the tissue. Thus, the sensor tip registers spatial variations in prostate tissue histology, both directly below and lateral to the tip itself. These findings indicate that tumours around the sensor tip could be detected, which in turn supports the idea of a future resonance-sensor-based clinical device for detecting tumours and for guiding biopsies.

Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

Applanation resonance tonometry for intraocular pressure in humans.

Glaucoma is a group of diseases associated with optic nerve damage and loss of visual field. The aetiology is not completely understood, but one of the major risk factors is elevated intraocular pressure (IOP). Reliable methods for measuring the IOP are therefore important. The aim of the study was to investigate the ability of the applanation resonance tonometry (ART) system, based on continuous force and area recording, to measure IOP in humans. Both the phase of initial indentation (IOPIndentation) and the phase when the sensor was removed (IOPRemoval) from the cornea were analysed. The Goldmann applanation tonometry (GAT) was used as reference method. The study included 24 healthy volunteers with normal IOP and 24 patients with elevated IOP. The correlation and standard deviation (SD) between IOPIndentation and IOPGAT was R = 0.92 (p < 0.001), SD = 3.6 mmHg, n = 104, and between IOPRemoval and IOPGAT R = 0.94 (p < 0.001), SD = 3.1 mmHg, n = 104. In conclusion, resonance sensor technology has made it possible to introduce a new multi-point method for measuring IOP, and the method is relevant for measuring IOP in humans. The study indicates that with further development towards elimination of position dependence, the ART has the potential to become a useful clinical instrument for IOP measurement.

An applanation resonator sensor for measuring intraocular pressure using combined continuous force and area measurement.

PURPOSE: For diagnostic purposes and for follow-up after treatment, it is important to have simple and reliable methods for measuring intraocular pressure (IOP). The purpose of this study was to develop a new applanation method for IOP measurement that uses combined continuous force and area measurement and to develop and evaluate an applanation resonator sensor (ARS) tonometer based on that method. METHODS: The tonometer was developed and evaluated in an in vitro porcine eye model, in which enucleated eyes were pressurized with a saline column. A model assuming that the applanation principle is valid over a certain interval of contact area was proposed. Continuous contact area was measured with a resonator sensor device, and contact force was measured with a force transducer, both mounted together in one probe. Reference IOP was measured in the vitreous chamber (IOP(VC)) with a standard fluid pressure transducer. RESULTS: An optimization algorithm determined the applanation interval that was optimal for calculating IOP(ARS). The corresponding time interval was 30 +/- 3 to 77 +/- 4 ms (mean +/- SD, n = 418) after initial contact. The proposed model showed a degree of explanation of R(2 [supi]) = 0.991 (n = 410, six eyes), corresponding to a correlation of r = 0.995 (n = 410) between IOP(ARS) and IOP(VC). The within-eyes precision (i.e., 95% confidence interval for the residuals between IOP(ARS) and IOP(VC)) was +/- 1.8 mm Hg (n = 410, six eyes). CONCLUSIONS: In this study, the ARS method for measuring IOP was evaluated in an in vitro porcine eye model and showed high precision. The ARS method is, to the authors' knowledge, the first to combine simultaneous, continuous sampling of both parameters included in the applanation principle: force and area. Consequently, there is a potential for reducing errors in clinical IOP tonometry.