For stroke and traumatic brain injury (TBI) patients minimizing the time from stroke onset/accide... more For stroke and traumatic brain injury (TBI) patients minimizing the time from stroke onset/accident to treat-ment is fundamental to increase the chances of achieving good clinical outcome. For patients with ischemic stroke thrombolytic treatment may be effective, but only 1–8% receive this treatment due to delays in seeking medical attention and late diagnosis. TBI patients with severe injury require immediate transportation to a trauma cen-ter. Microwave technology (MWT) has potential to be used for prehospital diagnosis of stroke and TBI patients by detecting intracranial bleedings and thereby make pre-hospital thrombolysis for stroke patients possible and increase triage accuracy for TBI patients. Methods Two clinical trials enrolling 20 + 25 stroke patients per-
Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 2,
2021 IEEE/ACM 1st Workshop on AI Engineering - Software Engineering for AI (WAIN)
Using machine learning in clinical practice poses hard requirements on explainability, reliabilit... more Using machine learning in clinical practice poses hard requirements on explainability, reliability, replicability and robustness of these systems. Therefore, developing reliable software for monitoring critically ill patients requires close collaboration between physicians and software engineers. However, these two different disciplines need to find own research perspectives in order to contribute to both the medical and the software engineering domain. In this paper, we address the problem of how to establish a collaboration where software engineering and medicine meets to design robust machine learning systems to be used in patient care. We describe how we designed software systems for monitoring patients under carotid endarterectomy, in particular focusing on the process of knowledge building in the research team. Our results show what to consider when setting up such a collaboration, how it develops over time and what kind of systems can be constructed based on it. We conclude that the main challenge is to find a good research team, where different competences are committed to a common goal.
Microwave technology has the potential to revolutionize how, when, and what care can be delivered... more Microwave technology has the potential to revolutionize how, when, and what care can be delivered to patients with acute, life-threatening medical conditions. The prospects are that microwave systems can both improve diagnostic ability and accuracy and enable earlier diagnosis. Early diagnosis is a key factor in acute situations, especially when breathing and circulation are affected. Conventional imaging modalities used for diagnostics, such as magnetic resonance imaging (MRI) and X-ray computed tomography (CT), are powerful but normally available only at hospitals.
Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assum... more Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assume a linear and time-invariant (LTI) mapping from sudomotor nerve (SN) activity to observed SCR. These LTI assumptions have previously been validated indirectly, by quantifying how much variance in SCR elicited by sensory stimulation is explained under an LTI model. This approach, however, collapses sources of variability in the nervous and effector organ systems. Here, we directly focus on the SN/SCR mapping by harnessing two invasive methods. In an intraneural recording experiment, we simultaneously track SN activity and SCR. This allows assessing the SN/SCR relationship but possibly suffers from interfering activity of non-SN sympathetic fibers. In an intraneural stimulation experiment under regional anesthesia, such influences are removed. In this stimulation experiment, about 95% of SCR variance is explained under LTI assumptions when stimulation frequency is below 0.6 Hz. At higher frequencies, nonlinearities occur. In the intraneural recording experiment, explained SCR variance is lower, possibly indicating interference from non-SN fibers, but higher than in our previous indirect tests. We conclude that LTI systems may not only be a useful approximation but in fact a rather accurate description of biophysical reality in the SN/SCR system, under conditions of low baseline activity and sporadic external stimuli. Intraneural stimulation under regional anesthesia is the most sensitive method to address this question.
Traumatic brain injury (TBI) is the leading cause of death and disability among young persons. A ... more Traumatic brain injury (TBI) is the leading cause of death and disability among young persons. A key to improve outcome for patients with TBI is to reduce the time from injury to definitive care by achieving high triage accuracy. Microwave technology (MWT) allows for a portable device to be used in the pre-hospital setting for detection of intracranial hematomas at the scene of injury, thereby enhancing early triage and allowing for more adequate early care. MWT has previously been evaluated for medical applications including the ability to differentiate between hemorrhagic and ischemic stroke. The purpose of this study was to test whether MWT in conjunction with a diagnostic mathematical algorithm could be used as a medical screening tool to differentiate patients with traumatic intracranial hematomas, chronic subdural hematomas (cSDH), from a healthy control (HC) group. Twenty patients with cSDH and 20 HC were measured with a MWT device. The accuracy of the diagnostic algorithm wa...
Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden senso... more Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden sensory stimuli (ie, arousal) have revealed 2 intraindividually reproducible response profiles in healthy young males that predict different neural and blood pressure responses to more sustained stress. Approximately 50% of subjects inhibit muscle sympathetic nerve activity during arousal, whereas the remaining 50% do not, and the latter group displays a markedly greater blood pressure increase in response to arousal, as well as during and after 3 minutes of mental arithmetic. Studying a group of monozygotic twins (10 pairs, 2 excluded from analysis), the aim of the present study was to evaluate the degree of genetic determination of these sympathetic response profiles. Muscle sympathetic burst incidence at rest was similar in twins, with a within-pair burst incidence ratio of 0.87±0.02 (SEM) compared with 0.73±0.07 found in unrelated pairs ( P =0.002), confirming a previous study from our la...
Medical & biological engineering & computing, Jan 13, 2016
Traumatic brain injury is the leading cause of death and severe disability for young people and a... more Traumatic brain injury is the leading cause of death and severe disability for young people and a major public health problem for elderly. Many patients with intracranial bleeding are treated too late, because they initially show no symptoms of severe injury and are not transported to a trauma center. There is a need for a method to detect intracranial bleedings in the prehospital setting. In this study, we investigate whether broadband microwave technology (MWT) in conjunction with a diagnostic algorithm can detect subdural hematoma (SDH). A human cranium phantom and numerical simulations of SDH are used. Four phantoms with SDH 0, 40, 70 and 110 mL are measured with a MWT instrument. The simulated dataset consists of 1500 observations. Classification accuracy is assessed using fivefold cross-validation, and a validation dataset never used for training. The total accuracy is 100 and 82-96 % for phantom measurements and simulated data, respectively. Sensitivity and specificity for bl...
Publisher Summary Microneurography enables neurophysiologists to record the action potentials, fr... more Publisher Summary Microneurography enables neurophysiologists to record the action potentials, from myelinated and unmyelinated efferent, and afferent nerve fibers in awakened human subjects, via tungsten microelectrodes inserted percutaneously into the peripheral nerves. Recording of postganglionic sympathetic nerve traffic has become the most common application of microneurography and has been largely used. However, microneurography is of limited use, when investigating neurological syndromes, entailing a loss of sympathetic nerve fibers/activity. In general, the technical difficulty and the invasiveness of intraneural recording continue to limit its use in the clinical investigations of autonomic disorders, but the technique remains essential for the elucidation of neural mechanisms in human autonomic pathology as well as it remains predominantly a research tool in controlled studies comparing the groups of patients/subjects. It rarely proves useful, as a diagnostic tool, in individual patients. This chapter uses two examples of neurological disorders in humans— namely, central and peripheral nerve injury —to illustrate how microneurography may contribute to the differentiation between neural and effector organ dysfunction in autonomic disorders, especially when performed in parallel, with other techniques, evaluating the autonomic nervous system.
The interaction between sympathetic vasoconstrictor activity to muscles (MSNA; burst frequency (B... more The interaction between sympathetic vasoconstrictor activity to muscles (MSNA; burst frequency (BF); burst incidence (BI)) and different stress and somatosensory stimuli is still unclear. 18 healthy men (median age 28 years) underwent microneurography recordings from the peroneal nerve. MSNA was recorded during heat (HP) and cold pain (CP) alone as well as combined with different stress-tasks (mental arithmetic, singing; giving a speech). Additional 9 healthy men (median age 26 years) underwent the stimulation protocol with an additional control-task (thermal pain combined with listening to music) to evaluate possible attentional confounders. MSNA was significantly increased by cold and heat pain. Cold pain-evoked responses were smaller. The diastolic blood pressure followed the time course of MSNA while heart rate remained unchanged. The mental stress-tasks further increased MSNA and were sufficient to reduce pain while the control-task had no effect. MSNA activity correlated negatively with pain intensity and positively with analgesia. High blood pressure values were associated with lower pain intensity. Our study indicates an impact of central sympathetic drive on pain and pain control. This article is protected by copyright. All rights reserved.
2014 IEEE MTT-S International Microwave Workshop Series on RF and Wireless Technologies for Biomedical and Healthcare Applications (IMWS-Bio2014), 2014
Pre-hospital care for stroke and trauma remains one of the global challenges., Each year around 1... more Pre-hospital care for stroke and trauma remains one of the global challenges., Each year around 15 million people each year suffer a stroke. Only a small fraction of stroke patients who could benefit from thrombolytic treatment reach diagnosis and treatment in time. To increase this low figure we have developed microwave technology aiming to differentiate hemorrhagic from ischemic stroke patients in a pre-hospital setting.
Journal of applied physiology (Bethesda, Md. : 1985), 2002
In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but ou... more In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but our laboratory has shown that single muscle vasoconstrictor neurons primarily fire only once per cardiac interval, as in normal subjects (Elam M and Macefield VG. J Appl Physiol 91: 717-724, 2001; Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708-1713, 1999). In this study, we used patients with obstructive sleep apnea syndrome (OSAS) to test the hypothesis that this firing pattern is maintained in other states of sympathoexcitation. Unitary recordings were made from muscle vasoconstrictor neurons in eight awake OSAS patients. The average firing frequency of 12 units was 0.96 Hz and the firing probability 51%, similar to previous observations in CHF patients (0.98 Hz, 55%) but higher than in healthy subjects (0.40 Hz, 31%). However, the percentages of cardiac intervals in which neurons generated one, two, three, or four spikes were 59, 27, 10, and 3%...
Both decreased and increased sympathetic nerve activity has been suggested as a possible underlyi... more Both decreased and increased sympathetic nerve activity has been suggested as a possible underlying mechanism in inflammatory skin lesions. Modulation of sympathetic function has been proposed in the treatment of dermatitis. This case report describes the investigation strategy and normal findings in a case of dermatitis strictly confined to the median nerve territory, illustrating the need for specific tests of sympathetic function when pharmacological as well as physical sympatho-modulatory therapies are considered.
Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old pa... more Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old patient with reflex sympathetic dystrophy (allodynia, marked vasoconstriction in the ulnar part of the left hand) following Vth finger amputation. Skin sympathetic activity showed normal characteristics with a weak discharge at rest whereas bursts of impulses could be evoked by sympatho-excitatory stimuli. Sympathetic bursts induced by painful stimuli were few, also during long-lasting allodynic pain. Sympathetic bursts induced by inspiratory gasps were not associated with excacerbation of pain. The discrepancy between the marked skin vasoconstriction and the low resting sympathetic discharge underlines the fact that sympathetic effector organ hyperactivity (i.e. vasoconstriction and/or hyperhidrosis) cannot be taken as evidence for increased sympathetic discharge. In the present case, the neuropathic pain syndrome cannot be considered as maintained by an increased sympathetic neural disch...
For stroke and traumatic brain injury (TBI) patients minimizing the time from stroke onset/accide... more For stroke and traumatic brain injury (TBI) patients minimizing the time from stroke onset/accident to treat-ment is fundamental to increase the chances of achieving good clinical outcome. For patients with ischemic stroke thrombolytic treatment may be effective, but only 1–8% receive this treatment due to delays in seeking medical attention and late diagnosis. TBI patients with severe injury require immediate transportation to a trauma cen-ter. Microwave technology (MWT) has potential to be used for prehospital diagnosis of stroke and TBI patients by detecting intracranial bleedings and thereby make pre-hospital thrombolysis for stroke patients possible and increase triage accuracy for TBI patients. Methods Two clinical trials enrolling 20 + 25 stroke patients per-
Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 2,
2021 IEEE/ACM 1st Workshop on AI Engineering - Software Engineering for AI (WAIN)
Using machine learning in clinical practice poses hard requirements on explainability, reliabilit... more Using machine learning in clinical practice poses hard requirements on explainability, reliability, replicability and robustness of these systems. Therefore, developing reliable software for monitoring critically ill patients requires close collaboration between physicians and software engineers. However, these two different disciplines need to find own research perspectives in order to contribute to both the medical and the software engineering domain. In this paper, we address the problem of how to establish a collaboration where software engineering and medicine meets to design robust machine learning systems to be used in patient care. We describe how we designed software systems for monitoring patients under carotid endarterectomy, in particular focusing on the process of knowledge building in the research team. Our results show what to consider when setting up such a collaboration, how it develops over time and what kind of systems can be constructed based on it. We conclude that the main challenge is to find a good research team, where different competences are committed to a common goal.
Microwave technology has the potential to revolutionize how, when, and what care can be delivered... more Microwave technology has the potential to revolutionize how, when, and what care can be delivered to patients with acute, life-threatening medical conditions. The prospects are that microwave systems can both improve diagnostic ability and accuracy and enable earlier diagnosis. Early diagnosis is a key factor in acute situations, especially when breathing and circulation are affected. Conventional imaging modalities used for diagnostics, such as magnetic resonance imaging (MRI) and X-ray computed tomography (CT), are powerful but normally available only at hospitals.
Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assum... more Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assume a linear and time-invariant (LTI) mapping from sudomotor nerve (SN) activity to observed SCR. These LTI assumptions have previously been validated indirectly, by quantifying how much variance in SCR elicited by sensory stimulation is explained under an LTI model. This approach, however, collapses sources of variability in the nervous and effector organ systems. Here, we directly focus on the SN/SCR mapping by harnessing two invasive methods. In an intraneural recording experiment, we simultaneously track SN activity and SCR. This allows assessing the SN/SCR relationship but possibly suffers from interfering activity of non-SN sympathetic fibers. In an intraneural stimulation experiment under regional anesthesia, such influences are removed. In this stimulation experiment, about 95% of SCR variance is explained under LTI assumptions when stimulation frequency is below 0.6 Hz. At higher frequencies, nonlinearities occur. In the intraneural recording experiment, explained SCR variance is lower, possibly indicating interference from non-SN fibers, but higher than in our previous indirect tests. We conclude that LTI systems may not only be a useful approximation but in fact a rather accurate description of biophysical reality in the SN/SCR system, under conditions of low baseline activity and sporadic external stimuli. Intraneural stimulation under regional anesthesia is the most sensitive method to address this question.
Traumatic brain injury (TBI) is the leading cause of death and disability among young persons. A ... more Traumatic brain injury (TBI) is the leading cause of death and disability among young persons. A key to improve outcome for patients with TBI is to reduce the time from injury to definitive care by achieving high triage accuracy. Microwave technology (MWT) allows for a portable device to be used in the pre-hospital setting for detection of intracranial hematomas at the scene of injury, thereby enhancing early triage and allowing for more adequate early care. MWT has previously been evaluated for medical applications including the ability to differentiate between hemorrhagic and ischemic stroke. The purpose of this study was to test whether MWT in conjunction with a diagnostic mathematical algorithm could be used as a medical screening tool to differentiate patients with traumatic intracranial hematomas, chronic subdural hematomas (cSDH), from a healthy control (HC) group. Twenty patients with cSDH and 20 HC were measured with a MWT device. The accuracy of the diagnostic algorithm wa...
Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden senso... more Microneurographic recordings of human muscle sympathetic nerve activity responses to sudden sensory stimuli (ie, arousal) have revealed 2 intraindividually reproducible response profiles in healthy young males that predict different neural and blood pressure responses to more sustained stress. Approximately 50% of subjects inhibit muscle sympathetic nerve activity during arousal, whereas the remaining 50% do not, and the latter group displays a markedly greater blood pressure increase in response to arousal, as well as during and after 3 minutes of mental arithmetic. Studying a group of monozygotic twins (10 pairs, 2 excluded from analysis), the aim of the present study was to evaluate the degree of genetic determination of these sympathetic response profiles. Muscle sympathetic burst incidence at rest was similar in twins, with a within-pair burst incidence ratio of 0.87±0.02 (SEM) compared with 0.73±0.07 found in unrelated pairs ( P =0.002), confirming a previous study from our la...
Medical & biological engineering & computing, Jan 13, 2016
Traumatic brain injury is the leading cause of death and severe disability for young people and a... more Traumatic brain injury is the leading cause of death and severe disability for young people and a major public health problem for elderly. Many patients with intracranial bleeding are treated too late, because they initially show no symptoms of severe injury and are not transported to a trauma center. There is a need for a method to detect intracranial bleedings in the prehospital setting. In this study, we investigate whether broadband microwave technology (MWT) in conjunction with a diagnostic algorithm can detect subdural hematoma (SDH). A human cranium phantom and numerical simulations of SDH are used. Four phantoms with SDH 0, 40, 70 and 110 mL are measured with a MWT instrument. The simulated dataset consists of 1500 observations. Classification accuracy is assessed using fivefold cross-validation, and a validation dataset never used for training. The total accuracy is 100 and 82-96 % for phantom measurements and simulated data, respectively. Sensitivity and specificity for bl...
Publisher Summary Microneurography enables neurophysiologists to record the action potentials, fr... more Publisher Summary Microneurography enables neurophysiologists to record the action potentials, from myelinated and unmyelinated efferent, and afferent nerve fibers in awakened human subjects, via tungsten microelectrodes inserted percutaneously into the peripheral nerves. Recording of postganglionic sympathetic nerve traffic has become the most common application of microneurography and has been largely used. However, microneurography is of limited use, when investigating neurological syndromes, entailing a loss of sympathetic nerve fibers/activity. In general, the technical difficulty and the invasiveness of intraneural recording continue to limit its use in the clinical investigations of autonomic disorders, but the technique remains essential for the elucidation of neural mechanisms in human autonomic pathology as well as it remains predominantly a research tool in controlled studies comparing the groups of patients/subjects. It rarely proves useful, as a diagnostic tool, in individual patients. This chapter uses two examples of neurological disorders in humans— namely, central and peripheral nerve injury —to illustrate how microneurography may contribute to the differentiation between neural and effector organ dysfunction in autonomic disorders, especially when performed in parallel, with other techniques, evaluating the autonomic nervous system.
The interaction between sympathetic vasoconstrictor activity to muscles (MSNA; burst frequency (B... more The interaction between sympathetic vasoconstrictor activity to muscles (MSNA; burst frequency (BF); burst incidence (BI)) and different stress and somatosensory stimuli is still unclear. 18 healthy men (median age 28 years) underwent microneurography recordings from the peroneal nerve. MSNA was recorded during heat (HP) and cold pain (CP) alone as well as combined with different stress-tasks (mental arithmetic, singing; giving a speech). Additional 9 healthy men (median age 26 years) underwent the stimulation protocol with an additional control-task (thermal pain combined with listening to music) to evaluate possible attentional confounders. MSNA was significantly increased by cold and heat pain. Cold pain-evoked responses were smaller. The diastolic blood pressure followed the time course of MSNA while heart rate remained unchanged. The mental stress-tasks further increased MSNA and were sufficient to reduce pain while the control-task had no effect. MSNA activity correlated negatively with pain intensity and positively with analgesia. High blood pressure values were associated with lower pain intensity. Our study indicates an impact of central sympathetic drive on pain and pain control. This article is protected by copyright. All rights reserved.
2014 IEEE MTT-S International Microwave Workshop Series on RF and Wireless Technologies for Biomedical and Healthcare Applications (IMWS-Bio2014), 2014
Pre-hospital care for stroke and trauma remains one of the global challenges., Each year around 1... more Pre-hospital care for stroke and trauma remains one of the global challenges., Each year around 15 million people each year suffer a stroke. Only a small fraction of stroke patients who could benefit from thrombolytic treatment reach diagnosis and treatment in time. To increase this low figure we have developed microwave technology aiming to differentiate hemorrhagic from ischemic stroke patients in a pre-hospital setting.
Journal of applied physiology (Bethesda, Md. : 1985), 2002
In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but ou... more In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but our laboratory has shown that single muscle vasoconstrictor neurons primarily fire only once per cardiac interval, as in normal subjects (Elam M and Macefield VG. J Appl Physiol 91: 717-724, 2001; Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708-1713, 1999). In this study, we used patients with obstructive sleep apnea syndrome (OSAS) to test the hypothesis that this firing pattern is maintained in other states of sympathoexcitation. Unitary recordings were made from muscle vasoconstrictor neurons in eight awake OSAS patients. The average firing frequency of 12 units was 0.96 Hz and the firing probability 51%, similar to previous observations in CHF patients (0.98 Hz, 55%) but higher than in healthy subjects (0.40 Hz, 31%). However, the percentages of cardiac intervals in which neurons generated one, two, three, or four spikes were 59, 27, 10, and 3%...
Both decreased and increased sympathetic nerve activity has been suggested as a possible underlyi... more Both decreased and increased sympathetic nerve activity has been suggested as a possible underlying mechanism in inflammatory skin lesions. Modulation of sympathetic function has been proposed in the treatment of dermatitis. This case report describes the investigation strategy and normal findings in a case of dermatitis strictly confined to the median nerve territory, illustrating the need for specific tests of sympathetic function when pharmacological as well as physical sympatho-modulatory therapies are considered.
Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old pa... more Intraneural recording in skin fascicles of the left ulnar nerve was performed in a 51 year old patient with reflex sympathetic dystrophy (allodynia, marked vasoconstriction in the ulnar part of the left hand) following Vth finger amputation. Skin sympathetic activity showed normal characteristics with a weak discharge at rest whereas bursts of impulses could be evoked by sympatho-excitatory stimuli. Sympathetic bursts induced by painful stimuli were few, also during long-lasting allodynic pain. Sympathetic bursts induced by inspiratory gasps were not associated with excacerbation of pain. The discrepancy between the marked skin vasoconstriction and the low resting sympathetic discharge underlines the fact that sympathetic effector organ hyperactivity (i.e. vasoconstriction and/or hyperhidrosis) cannot be taken as evidence for increased sympathetic discharge. In the present case, the neuropathic pain syndrome cannot be considered as maintained by an increased sympathetic neural disch...
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