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Bram Platel

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Bram Platel

  1. 1. Exploring the uncharted Deep Brain Stimulation investigated with dMRI dr. ir. Bram Platel ir. Ellen Brunenberg prof. dr.Veerle Visser-Vandewalle
  2. 2. Deep Brain Stimulation Deep Brain Stimulation (DBS) is type of neuro-modulation. It is a neuro-surgical treatment, in which an electrode is implanted in a specific part of the brain. Through impulses it receives from a stimulator it disables that part of the brain.
  3. 3. Electrode Sub-Thalamic Nucleus (STN) Stimulator
  4. 4. Up to now over 40.000 people have been treated with DBS world wide Electrode Sub-Thalamic Nucleus (STN) Stimulator
  5. 5. no DBS
  6. 6. no DBS DBS on
  7. 7. Side effects
  8. 8. Change in behavior In more than 50% of the treated patients a change in behavior is noticed* Stim Off Stim On 41% cognitive side effects 8% depression 4% mania *Temel et al. “Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review” Stim On Stim Off Bejjani et al. “Transient acute depression induced by high-frequency deep-brain stimulation”
  9. 9. Cause of the side effects The cause of the side effects might be that stimulation is not limited to the motor part of the STN* [Hamani et al.] *Temel et al. Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review
  10. 10. Locating the STN
  11. 11. Locating the STN Anterior Commissure Posterior Commissure
  12. 12. Locating the STN Anterior Commissure Posterior Commissure
  13. 13. Research Goal Y. Temel et al. / Progress in Neurobiology 76 (2005) 393–413 399 *Temel et al. “The functional role of the subthalamic nucleus in cognitive and limbic circuits “ [Hamani et al.] Fig. 3. Schematic illustration of the primate basal ganglia-thalamocortical associative, limbic and motor circuits. The STN has a central position in each of these circuits. Associative circuit: the two associative circuits are the dorsolateral prefrontal circuit (DPC) and lateral orbitofrontal circuit (LOC), which are initiated from the dorsolateral prefrontal cortex (DLPC), and lateral orbitofrontal cortex (LOFC), respectively. The second station is the dorsolateral head and the rostrocaudal axis of the caudate nucleus. From here, this circuit is directed to the dorsomedial part of the GPi and to the rostral region of the SNr and to the anterior parts of the GPe. The GPi and SNr project to the VA and CM nuclei of the thalamus and the DPC is closed by the thalamocortical pathway back to the DLPC and the LOC back to the LOFC. This pathway is also known as the direct pathway. From the GPe, a projection to the STN and GPi/SNr exists. This pathway is also known as the indirect pathway. The STN is anatomically connected with both direct, through its projection to the GPi and SNr, and indirect pathway, through its projection to the GPe. Limbic circuit: projections from the hippocampus, the amygdala, limbic and paralimbic cortices are primarily concentrated at the level of the ventral striatum. The ventral striatum consists basically of the nucleus accumbens, ventromedial part of the caudate-putamen and the medium-celled portion of the olfactory tubercle. The ventral striatum projects in turn to the ventral pallidum (VP). From here the limbic circuit is directed to the MD nucleus of the thalamus. This circuit is closed by a thalamocortical pathway to the anterior cingulated area and medial orbitofrontal cortex. The STN has reciprocal connections with the ventral pallidum. The ventral pallidum is
  14. 14. Research Goal Y. Temel et al. / Progress in Neurobiology 76 (2005) 393–413 399 *Temel et al. “The functional role of the subthalamic nucleus in cognitive and limbic circuits “ [Hamani et al.] Using neurological pathways to localize the Fig. 3. Schematic illustration of the primate basal ganglia-thalamocortical associative, limbic and motor circuits. The STN has a central position in each of these circuits. Associative circuit: the two associative circuits are the dorsolateral prefrontal circuit (DPC) and lateral orbitofrontal circuit (LOC), which are initiated from the dorsolateral prefrontal cortex (DLPC), and lateral orbitofrontal cortex (LOFC), respectively. The second station is the dorsolateral head and the rostrocaudal axis of the caudate nucleus. From here, this circuit is directed to the dorsomedial part of the GPi and to the rostral region of the SNr and to the anterior parts of the GPe. The STN and to subdivide it into a motor, limbic and GPi and SNr project to the VA and CM nuclei of the thalamus and the DPC is closed by the thalamocortical pathway back to the DLPC and the LOC back to the LOFC. This pathway is also known as the direct pathway. From the GPe, a projection to the STN and GPi/SNr exists. This pathway is also known as the indirect pathway. The STN is anatomically connected with both direct, through its projection to the GPi and SNr, and indirect pathway, through its projection to the GPe. Limbic circuit: projections from the hippocampus, the amygdala, limbic and paralimbic cortices are primarily concentrated at the level of the ventral striatum. The ventral striatum associative part. consists basically of the nucleus accumbens, ventromedial part of the caudate-putamen and the medium-celled portion of the olfactory tubercle. The ventral striatum projects in turn to the ventral pallidum (VP). From here the limbic circuit is directed to the MD nucleus of the thalamus. This circuit is closed by a thalamocortical pathway to the anterior cingulated area and medial orbitofrontal cortex. The STN has reciprocal connections with the ventral pallidum. The ventral pallidum is considered to be the major limbic circuit output region. Modulation of the STN neuronal discharge directly influences the activity of both NMDA and non-NMDA expressing neurons in the VP. Within this concept of the limbic circuit, the STN again has a pivotal role as it is directly connected with the output of this circuit. Motor circuit: the cortical input to the motor circuit originates mainly from the primary motor, premotor and somatosensory areas. This somatotopic glutamatergic input is largely directed to the putamen, which projects topographically to the motor parts (ventrolateral (VL) and posterior) of the GPe and GPi and the SNr. From the GPe, a pathway projects to the STN. The STN mainly projects to the GPi and SNr. The SNr and the GPi serve as the output nuclei of the basal ganglia. The thalamic areas involved in the motor circuit are mainly the VL, ventroanterior (VA) and the centromedian nucleus (CM). This loop is closed by means of the thalamic projection (glutamatergic) to the cortical areas.
  15. 15. White matter [Williams et al.]
  16. 16. Diffusion MRI to visualize white matter connections
  17. 17. Anatomical scan & FA-map T2 anatomical scan, with FA inlay FA map with Paxinos & Watson Atlas PhD project Ellen Brunenberg
  18. 18. Anatomical scan & FA-map T2 anatomical scan, with FA inlay FA map with Paxinos & Watson Atlas PhD project Ellen Brunenberg
  19. 19. DTI vs HARDI DTI HARDI Crossing of the Corpus Callosum with the Corona Radiata
  20. 20. DTI vs HARDI DTI HARDI Crossing of the Corpus Callosum with the Corona Radiata
  21. 21. DTI vs HARDI DTI HARDI Crossing of the Corpus Callosum with the Corona Radiata
  22. 22. DTI vs HARDI DTI HARDI Crossing of the Corpus Callosum with the Corona Radiata
  23. 23. DTI vs HARDI DTI HARDI Crossing of the Corpus Callosum with the Corona Radiata
  24. 24. DTI and HARDI in STN DTI super quadrics HARDI Q-ball glyphs with atlas [Brunenberg et al. “Untangling a Fiber Bundle Knot”]
  25. 25. DTI and HARDI in STN DTI super quadrics HARDI Q-ball glyphs with atlas [Brunenberg et al. “Untangling a Fiber Bundle Knot”]
  26. 26. postmortem brein
  27. 27. postmortem brein 3T MRI scanner
  28. 28. postmortem brein 3T MRI scanner small cube around the STN
  29. 29. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner
  30. 30. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner difusion images
  31. 31. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner difusion images microtome
  32. 32. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner difusion images microtome histological staining
  33. 33. postmortem brein 3T MRI scanner small cube around the STN 9.4 T MRI scanner difusion images validation microtome histological staining 3D reconstruction
  34. 34. Translation to the patient The detailed findings of the post-mortem scans have to be translated to regular dMRI patient data. • Lower resolution • Lower SNR • Different Orientation / Shape
  35. 35. Benefits of the research • Reduction of side effects • More effective stimulation • Reduced planning and surgery time But also: • Insight in the connectivity of the nuclei • This may lead to improved stimulation targets
  36. 36. BME ME
  37. 37. BME ME

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