•One complete, postmortem human brainstem was scanned with MRI for 208 h.•Anatomic and diffusion images achieved isotropic resolutions of 50 and 200 μm.•Ninety gray and white matter structures were ...manually segmented in the brainstem.•Diffusion tractography was used to reconstruct 11 unique brainstem tracts.•Data are rendered into a high-resolution, interactive 3D atlas available online.
Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in liquid fluorocarbon. MRI was performed in a 7-Tesla scanner with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 h and 208 h, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy. Anatomic and diffusion images were rendered with isotropic resolutions of 50 μm and 200 μm, respectively. Ninety different structures were segmented and labeled, and 11 different fiber bundles were rendered with tractography. The complete atlas is available online for interactive use at https://www.civmvoxport.vm.duke.edu/voxbase/login.php?return_url=%2Fvoxbase%2F. This atlas presents multiple contrasting datasets and selected tract reconstruction with unprecedented resolution for MR imaging of the human brainstem. There are immediate applications in neuroanatomical education, with the potential to serve future applications for neuroanatomical research and enhanced neurosurgical planning through “safe” zones of entry into the human brainstem.
Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular ...schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.
The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.
Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.
SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.
Abstract
BACKGROUND
Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible.
OBJECTIVE
To evaluate the ...role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project.
METHODS
A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively.
RESULTS
Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure.
CONCLUSION
GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
Graphical Abstract
Graphical Abstract
•Obstacles for CED of CAR T cells are sedimentation, tube clogging, low viability.•LV Hydrogel is a biodegradable hyaluronic acid based biomaterial.•LV Hydrogel provides 20-fold increase in the ...delivery rate of CAR T cells.•Migration capacity and cytotoxicity of CAR T cells remain the same after infusion.•LV hydrogel has no toxic effect on rodent brain and fully disintegrated after 2 weeks.
Convection Enhanced Delivery (CED) infuses therapeutic agents directly into the intracranial area continuously under pressure. The convection improves the distribution of therapeutics such as those aimed at brain tumors. Although CED successfully delivers small therapeutic agents, this technique fails to effectively deliver cells largely due to cell sedimentation during delivery. To overcome this limitation, we have developed a low viscosity hydrogel (LVHydrogel), which is capable of retaining cells in suspension. In this study, we evaluated whether LVHydrogel can effectively act as a carrier for the CED of tumor-specific chimeric antigen receptor (CAR) T cells. CAR T cells were resuspended in saline or LVHydrogel carriers, loaded into syringes, and passed through the CED system for 5 h. CAR T cells submitted to CED were counted and the efficiency of delivery was determined. In addition to delivery, the ability of CAR T cells to migrate and induce cytotoxicity was evaluated. Our studies demonstrate that LVHydrogel is a superior carrier for CED in comparison to saline. The efficiency of cell delivery in saline carrier was only ∼3–5% of the total cells whereas delivery by the LVHydrogel carrier was much higher, reaching ∼45–75%. Migration and Cytotoxicity was similar in both carriers in non-infused samples but we found superior cytotoxicity in LVHydrogel group post-infusion. We demonstrate that LVHydrogel, a biodegradable biomaterial which does not cause acute toxicity on preclinical animal models, prevents cellular sedimentation during CED and presents itself as a superior carrier to the current carrier, saline, for the CED of CAR T cells.
Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, ...retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors.
The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated.
The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022).
Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.
Abstract
Breast cancer may cause distant metastasis even though there is no local recurrence. Disease can spread to any part of body via lymphoid and hematogenous way, and clivus is one of the most ...common locations. Total excision of clival lesions carries a significant risk of neurologic damage due to proximity to cranial nerves. We present 62-year-old woman who has a previously known breast cancer history. She admitted to our clinic with unilateral sixth nerve palsy and diplopia. Imaging studies revealed clivus metastasis. Patient was treated with gamma knife radiosurgery. In the next 2 months, sixth nerve palsy recovered along with diplopia. In this case report we would like to emphasize the importance of gamma knife radiosurgery at the deeply located breast cancer metastasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
INTRODUCTION
Traditional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology or the low spatial resolution of magnetic ...resonance imaging (MRI). Magnetic resonance histology (MRH) uses postmortem high-resolution MRI to circumvent the challenges associated with both modalities.
METHODS
A human brainstem specimen extending from the rostral diencephalon through the caudal medulla was removed from a 65-year-old male within 24 hours of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in buffered liquid fluorocarbon. MRI was performed in a 7-Tesla machine with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 hours and 208 hours, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy.
RESULTS
Anatomic and diffusion images were rendered with isotropic resolutions of 50 μm and 200 μm, respectively. Spatial resolution was high enough to visualize individual fasciculi of the descending corticospinal tracts intercalated between the transverse pontocerebellar fibers. Ninety different structures were segmented and 11 different fiber bundles were rendered with tractography. Angular resolution was high enough to visualize crossing fibers, such as those of the superior cerebellar peduncle. Both gray and white matter can be visualized in 3D simultaneously, such as the subthalamic nuclei and corticospinal tracts, as may be used in deep brain stimulation.
CONCLUSION
We used MRH to enable unprecedented resolution in digital imaging of the human brainstem and adjacent diencephalic structures, and we then performed comprehensive segmentation and tractography to render an interactive, three-dimensional atlas of both gray and white matter. This atlas has immediate applications in neuroanatomical study and education, with the potential for future neurosurgical applications in enhancing neurosurgical planning through “safe” zones of entry into the human brainstem. We are currently building the computer infrastructure to make this atlas publicly-available.
Objective. In bilateral cleft lip, there is a characteristic deformity called cleft lip nose characterized by short columella and prolabium with a pressed nose. Although lots of surgical techniques ...were described for columella lengthening and correction of the nose deformity, no technical method was suggested for prolabium lengthening.
Study Design. In this paper we propose a simultaneous bilateral cleft lip repair and lengthening of the prolabium, and describe a new technique called “Turkish tulip” for this aim.
Patients and Method. Eleven patients (6 males and 5 females) with bilateral cleft lip were treated using this method. Patients' ages ranged from 3 months to 17 years at the time of operation. Five patients had incomplete and six had complete bilateral cleft lips. The patients were evaluated in terms of functional and aesthetic results in postoperative period.
Results. The average follow‐up time was 8 months (ranged from 4 months to 15 months). There were no postoperative complications. The prolabium was lengthened adequately in all patients. No notch and whistle deformity was seen in our series. The patient or parent satisfaction was good or perfect in all cases.
Conclusions. To avoid the disadvantage of the long time course required to correct the nose deformity and to lengthen the prolabium, we propose the “Turkish tulip” technique with the primary repair of bilateral clef lips simultaneously. With this technique it is possible to lengthen the columello‐prolabial complex with cleft lip repair in the same session without any intervention to any part of the nose including the columella. As a preliminary study, according to the early results, this new technique seems to have good cosmetic outcomes.
Vaccines against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) provide successful control of the coronavirus-2019 (COVID-19) pandemic. The safety and immunogenicity studies are ...encouraging in patients with inborn errors of immunity (IEI); however, data about mortality outcomes and severe disease after vaccination still need to be fully addressed. Therefore, we aimed to determine the clinical and immunological outcomes of SARS-CoV-2 infection in patients with IEI who have received vaccination.
Eighty-eight patients with a broad range of molecular etiologies were studied; 45 experienced SARS-CoV-2 infection. Infection outcomes were analyzed in terms of genetic etiology, background clinical characteristics, and immunization history, including the type and number of doses received and the time elapsed since vaccination. In addition, anti-SARS-CoV-2 antibodies were quantified using electrochemiluminescent immunoassay.
Patients were immunized using one of the three regimens: inactivated (Sinovac, Coronavac®), mRNA (BNT162b2, Comirnaty®, Pfizer-Biontech), and a combination. All three regimens induced comparable anti-SARS-CoV-2 IgG levels, with no differences in the adverse events. Among 45 patients with COVID-19, 26 received a full course of vaccination, while 19 were vaccine-naive or received incomplete dosing. No patients died due to COVID-19 infection. The fully immunized group had a lower hospitalization rate (23% vs. 31.5%) and a shorter symptomatic phase than the others. Among the fully vaccinated patients, serum IgM and E levels were significantly lower in hospitalized patients than non-hospitalized patients.
COVID-19 vaccines were well-tolerated by the IEI patients, and a full course of immunization was associated with lower hospitalization rates and a shorter duration of COVID-19 symptoms.
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