Jozsef Constantin Szeles

High-resolution blood flow velocity measurements in the human finger.

MR phase contrast blood flow velocity measurements in the human index finger were performed with triggered, nontriggered, and cine acquisition schemes. A strong (Gmax = 200 mT/m), small bore (inner diameter 12 cm) gradient system inserted in a whole body 3 Tesla MR scanner allowed high‐resolution imaging at short echo times, which decreases partial volume effects and flow artifacts. Arterial blood flow velocities ranging from 4.9–19 cm/sec were measured, while venous blood flow was significantly slower at 1.5–7.1 cm/sec. Taking into account the corresponding vessel diameters ranging from 800 μm to 1.8 mm, blood flow rates of 3.0–26 ml/min in arteries and 1.2–4.8 ml/min in veins are obtained. The results were compared to ultrasound measurements, resulting in comparable blood flow velocities in the same subjects. Magn Reson Med 45:716–719, 2001.

In vivo magnetic resonance micro-imaging of the human toe at 3 tesla

The feasibility of in vivo high-resolution magnetic resonance micro-imaging of fine anatomic structures of human toes was tested. Five healthy subjects were investigated on an experimental 3 Tesla whole body scanner, using standard 3D gradient echo sequences. A radio-frequency surface coil was used for signal detection. Feet, toes and surface coil were comfortably fixed using a home built device for positioning and reduction of motion artifacts. The spatial resolution of 117 x 313 x 375 microm(3) allowed detailed visualization of anatomic structures like skin layers, vessels and nerves. In addition, oval structures with diameters ranging from 500 to 1000 microm were observed in all subjects, which could represent the sensory nerve endings of Vater-Pacinian bodies. Thus, high resolution MR micro-imaging at 3 Tesla may provide improved morphologic information in distal extremities of humans in vivo.

Modulation of Muscle Tone and Sympathovagal Balance in Cervical Dystonia Using Percutaneous Stimulation of the Auricular Vagus Nerve.

Primary cervical dystonia is characterized by abnormal, involuntary, and sustained contractions of cervical muscles. Current ways of treatment focus on alleviating symptomatic muscle activity. Besides pharmacological treatment, in severe cases patients may receive neuromodulative intervention such as deep brain stimulation. However, these (highly invasive) methods have some major drawbacks. For the first time, percutaneous auricular vagus nerve stimulation (pVNS) was applied in a single case of primary cervical dystonia. Auricular vagus nerve stimulation was already shown to modulate the (autonomous) sympathovagal balance of the body and proved to be an effective treatment in acute and chronic pain, epilepsy, as well as major depression. pVNS effects on cervical dystonia may be hypothesized to rely upon: (i) the alteration of sensory input to the brain, which affects structures involved in the genesis of motoric and nonmotoric dystonic symptoms; and (ii) the alteration of the sympathovagal balance with a sustained impact on involuntary movement control, pain, quality of sleep, and general well-being. The presented data provide experimental evidence that pVNS may be a new alternative and minimally invasive treatment in primary cervical dystonia. One female patient (age 50 years) suffering from therapy refractory cervical dystonia was treated with pVNS over 20 months. Significant improvement in muscle pain, dystonic symptoms, and autonomic regulation as well as a subjective improvement in motility, sleep, and mood were achieved. A subjective improvement in pain recorded by visual analog scale ratings (0-10) was observed from 5.42 to 3.92 (medians). Muscle tone of the mainly affected left and right trapezius muscle in supine position was favorably reduced by about 96%. Significant reduction of muscle tone was also achieved in sitting and standing positions of the patient. Habituation to stimulation leading to reduced stimulation efficiency was observed and counteracted by varying stimulation patterns. Experimental evidence is provided for significantly varied sympathovagal modulation in response to pVNS during sleep, assessed via heart rate variability (HRV). Time domain measures like the root mean square of successive normal to normal heart beat intervals, representing parasympathetic (vagal) activity, increased from 37.8 to 67.6 ms (medians). Spectral domain measures of HRV also show a shift to a more pronounced parasympathetic activity.

Optic Visualization of Auricular Nerves and Blood Vessels: Optimisation and Validation

Auricular blood vessels can be visualized by transillumination of the auricular tissue. The optimisation and validation of the optic visualization are the main subject of this work. Since blood vessels and nerve fibers can be found along one another, the transillumination reveals locations of auricular nerves to unaided human eye. The visualization of the nerves is needed by physicians to precisely insert needles into the auricle for electrical stimulation of auricular nerves. The stimulation is applied to relieve chronic pain and normalize vital physiological parameters. Theoretical approaches are shortly considered which are related to light absorption coefficients of different auricular tissue types and coefficient changes over wavelength. The theory predicts optimal optical contrasts if green and blue colors of light are applied. An experimental validation has been carried out using a novel transillumination device, a finger thimble, among young and elderly, male and female; in total 22 volunteers. Complementary experimental approaches have confirmed theoretical reasoning and have been used to optimize the optical contrast and applied color mixture even further.

New approaches in multi-punctual percutaneous stimulation of the auricular vagus nerve

Electrical stimulation of the cervical vagus nerve is an established treatment for therapy refractory epilepsy and, more recently, for depression and congestive heart failure. To overcome risks in implantation of neurostimulation devices as well as to extend application areas, less invasive techniques have been developed affecting the auricular branch of the vagus nerve (ABVN). This includes transcutaneous and percutaneous stimulation at the concha, antihelix, or tragus region of the auricle. Current areas of treatment include epilepsy, mood disorders, chronic pain, and cardiovascular diseases. This paper discusses new methodological approaches in percutaneous ABVN stimulation applying adaptive stimulation patterns controlled by biofeedback. The biofeedback is established by the use of the heart rate variability, blood perfusion index, and muscle tone, all objective measures for therapeutic efficiency. Preliminary results provide evidence that these new approaches may lead to more effective treatment for chronic pain, chronic wounds, and movement disorders.

Expected Effects of Auricular Vagus Nerve Stimulation in Dystonia.

Punctual electrical stimulation of the auricular branch of the vagus nerve is a potentially effective, minimalinvasive treatment in primary dystonia. This is due to electrical stimulation effects on brain structures involved in the genesis of dystonia. Preliminary experimental data from stimulation with fixed patterns of three vagal points in the auricle reveals significant improvements in motility in cervical dystonia. Based on theoretical considerations, specific stimulation patterns are proposed here which account for the identified signal transduction pathways, neural plasticity and adaptation processes.

Histopathologic correlation of high-resolution magnetic resonance imaging of human cervical tissue samples at 3 tesla: validation of a technique.

Csapó B, Széles J, Helbich TH, et al. Histopathologic correlation of high resolution magnetic resonance imaging of human cervical tissue samples at 3 tesla: validation of a technique. Invest Radiol 2002;37:381–385. rationale and objectives. High-resolution magnetic resonance (HR-MR) images of human cervical tissue samples were correlated with low magnification histology to investigate the MR presentation of normal and pathologic anatomic structures in cervical tissue samples at 3T. methods. Tissue samples were obtained from five large loop excision of the transformation zone (LLETZ) cone biopsies and one surgical specimen. HR-MR images (3D-Spin Echo sequence: TR/TE: 1500/60 milliseconds, voxel size of 117 × 208 × 234 &mgr;m) and low magnification (5×) histology sections were acquired in the same anatomical planes and correlated. results. In vitro HR-MR imaging of cervical tissue samples correlated well with low magnification microscopic histology, demonstrating normal anatomy (epithelium and its mucus layer, connective tissue of the stroma, glands, blood vessels). In vitro HR-MR imaging adds information about tumor content and margins. conclusions. High resolution MR imaging of cervical tissue samples assists in the identification of both normal structures and pathologic changes.

Optic visualisation of auricular blood vessels

Optic visualization of auricular blood vessels is considered using transillumination. Since the vessels and nerves course alongside one another, the locations of the nerves are disclosed. The visualization of the nerves is needed for a precise needle application by physician within the scope of electrical stimulation of auricular nerves; the stimulation being applied for pain relieve. Theoretical approaches are considered based on light absorption coefficients over wavelength of different auricular tissue types, which predict optimal optical contrasts for green and blue light. Complementary experimental approaches are introduced which statistical results have proved theoretical reasoning.

Higuchi Fractal Dimension of Heart Rate Variability During Percutaneous Auricular Vagus Nerve Stimulation in Healthy and Diabetic Subjects

Analysis of heart rate variability (HRV) can be applied to assess the autonomic nervous system (ANS) sympathetic and parasympathetic activity. Since living systems are non-linear, evaluation of ANS activity is difficult by means of linear methods. We propose to apply the Higuchi fractal dimension (HFD) method for assessment of ANS activity. HFD measures complexity of the HRV signal. We analyzed 45 RR time series of 84 min duration each from nine healthy and five diabetic subjects with clinically confirmed long-term diabetes mellitus type II and with diabetic foot ulcer lasting more than 6 weeks. Based on HRV time series complexity analysis we have shown that HFD: (1) discriminates healthy subjects from patients with diabetes mellitus type II; (2) assesses the impact of percutaneous auricular vagus nerve stimulation (pVNS) on ANS activity in normal and diabetic conditions. Thus, HFD may be used during pVNS treatment, to provide stimulation feedback for on-line regulation of therapy in a fast and robust way.

Device development guided by user satisfaction survey on auricular vagus nerve stimulation

Abstract Development of wearable point-of-care medical devices faces many challenges. Besides technological and clinical issues, demands on robustness, miniaturization, and user interface design are of paramount importance. However, a systematic assessment of these non-functional but essential requirements is often impossible within the first product cycle. Later, surveys on user satisfaction with existing devices and user demands can offer significant input for device re-development and improvement. In this paper, we present a survey on satisfaction with and demands for a wearable medical device for percutaneous auricular vagus nerve stimulation (pVNS). We analyzed 36 responses from patients treated with pVNS and five responses from experienced physicians in order to devise a future concept of pVNS. Main shortcomings of a current pVNS device were identified to be lacking water resistance and mechanical robustness, both impairing daily activities. Painful sensation during pVNS application, unwanted side effects like skin irritations and strongly varying perception of the stimulation were reported. Results urge for more patient self-governance and an (automatic) adjustment of the stimulation to the current physiological state of the patient. Attained results support a strategic approach for future developments of pVNS towards personalized health care.