Non-invasively enhanced intracranial transplantation of mesenchymal stem cells using focused ultrasound mediated by overexpression of cell-adhesion molecules

Although there have been reports of promising results regarding the transplantation of mesenchymal stem cells (MSCs) for neurodegenerative diseases through the use of neuronal differentiation or control of the microenvironment, traditional surgical transplantation methods like parenchymal or intravenous injection have limitations such as secondary injuries in the brain, infection, and low survival rate of stem cells in the target site. Focused ultrasound (FUS) treatment is an emerging modality for the treatment of brain diseases, including neurodegenerative disorders. The various biological effects of FUS treatment have been investigated; therefore, the goal is now to improve the delivery efficiency and function of MSCs by capitalizing on the advantages of FUS. In this study, we demonstrated that FUS increases MSC transplantation into brain tissue by >2-fold, and that this finding might be related to the activation of intercellular adhesion molecule-1 in endothelial and subendothelial cells and vascular adhesion molecule-1 in endothelial cells.ope

Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons From the Past to Inform the Future

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.ope

Skull Factors Affecting Outcomes of Magnetic Resonance-Guided Focused Ultrasound for Patients With Essential Tremor

Purpose: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has become a standard treatment for medically intractable essential tremor (ET). Skull density ratio (SDR) and skull volume in patients with ET are currently considered useful indicators of the successful application of MRgFUS. We compared the clinical outcomes of MRgFUS thalamotomy with SDR above 0.4 and 0.45. We also described patterns of SDR and skull volume in Korean patients with ET who were eligible to be screened for MRgFUS. Materials and methods: In screening 318 ET patients, we evaluated patterns of skull density and skull volume according to age and sex. Fifty patients with ET were treated with MRgFUS. We investigated the effects of SDR and skull volume on treatment parameters and the outcomes of ET. Results: The mean SDR of the 318 ET patients was 0.45±0.11, and that for skull volume was 315.74±40.95 cm³. The male patients had a higher SDR than female patients (p=0.047). Skull volume significantly decreased with aging. SDR and skull volume exhibited a linear negative relationship. Among therapeutic parameters, maximal temperature was positively related to SDR, while sonication number was not related to either SDR or skull volume. Tremor outcome was also not related to SDR or skull volume. Conclusion: SDR varied widely from 0.11 to 0.73, and men had a higher SDR. Therapeutic parameters and clinical outcomes were not affected by SDR or skull volume.ope

Factors Related to Successful Energy Transmission of Focused Ultrasound Through a Skull : A Study in Human Cadavers and Its Comparison With Clinical Experiences

Objective: Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. Methods: For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. Results: Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). Conclusion: This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.ope

Analysis of the Non-diagnostic Results after Stereotactic Biopsy

Objective: Although stereotactic brain biopsy has played an important role in the diagnosis and management of brain lesions, there is a significant number of patients in whom a histologic diagnosis is not achieved. The non-diagnostic result of stereotactic biopsy poses a management dilemma. The goal of this study was to analyze the non-diagnostic results after stereotactic biopsy, subsequent management, progress and final diagnosis. Methods: The authors reviewed the clinical and radiological records of 158 patients who underwent stereotactic brain biopsies using Leksell stereotactic frame. We included 138 patients who were followed more than 6 months in this study. Results: The results were diagnostic in 118 cases and the overall diagnostic yield of the procedure was 85.6%. A definite histological diagnosis was not made in 20 patients: gliosis in 10, normal white matter in 5, necrosis in 2, infiltration of inflammatory cell in 2, and insufficient material in 1. The subsequent managements, progress and their final diagnoses were described. Conclusion: Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. Multiple serial biopsy, intraoperative histological diagnosis, and updated imaging-guided biopsy should be tried to minimize the sampling error. Clinical and radiological follow-up are essential for further diagnosis and management in non-diagnostic cases.ope

Defining the Interval between the Development of New Lesion on Follow Up Study and 1st Gamma Knife Radiosurgery without Whole-Brain Radiation Therapy in the Management of Brain Metastases

The aim of this retrospective study is to define the interval between the development of new lesion on follow up study and 1st gamma knife radiosurgery (GKS) without whole brain radiation therapy (WBRT) in the management of brain metastases. Between May 1992 and January 2006, 378 patients (207 males and 174 females) with brain metastases were treated with radiosurgery at the Yonsei University Medical Center. Reviewing the follow up study was available in 357 (81.7%) cases, and new lesions were found in 83 (23.2%) cases. We classified the development of new lesions after 1st GKS as missed, invisible, true new and undetermined lesions；missed lesions are those which were visible on MRI at the time of 1st GKS retrospectively, but omitted；invisible lesions, too small to be visualized on MRI at the time of 1st GKS, may be less than 1mm in size at that time and will be new lesions, visible on MRI within 4months after 1st GKS；true new lesions, newly metastasized to brain after GKS, developed 8 months after 1st GKS； undetermined lesions, new lesions developed 5 to 7 months after 1st GKS. There were 12 patients (18.18%) of missed lesions, and the number of those lesions was 17；10 patients (15.15%) of invisible, and the number, 51；25 patients (37.88%) of undetermined, and the number, 166；19 patients (28.79%) of true new lesions, and the number, 100. The incidence of new lesion development was high between 5th and 7th months after GKS, and after that, it decreased suddenly. And that low incidence was even after 7th months. GKS without adjuvant WBRT showed good effect, however, strict MRI follow up at 4 and 7months after GKS is necessary to detect and treat the invisible and missed lesions.ope