Endosteal Layer Research Articles

A rare entity of primary hydatid cyst located between the two laiers of the intracranial dura in a child: a case report

Background: Hydatid disease is a parasitic infection caused by the tapeworm Echinococcus granulosus. Intracranial hydatid cysts are rare and account for less than 3% of all cases of hydatid disease. Typically, these cysts are found in the intracerebral spaces. However, this study presents an extremely rare intradural hydatid cyst. Case Presentation: This study presents the case of an 8-year-old boy presented with a 3-month history of headache and vomiting without any neurological deficit. Full radiological investigations were performed, and only brain magnetic resonance imaging showed a large cerebral hydatid cyst located within the dura layers between the periosteal and the endosteal layers. Surgery was performed without cyst rupture, confirming the intracerebral intradural location. Conclusion: Early diagnosis and treatment for intracranial hydatid cysts are crucial to prevent complications such as neurological deficits, seizures, and even death. In this case, the intracerebral intradural location of the cyst is extremely rare.

A rare entity of primary hydatid cyst located between the two laiers of the intracranial dura in a child: a case report

Background: Hydatid disease is a parasitic infection caused by the tapeworm Echinococcus granulosus. Intracranial hydatid cysts are rare and account for less than 3% of all cases of hydatid disease. Typically, these cysts are found in the intracerebral spaces. However, this study presents an extremely rare intradural hydatid cyst. Case Presentation: This study presents the case of an 8-year-old boy presented with a 3-month history of headache and vomiting without any neurological deficit. Full radiological investigations were performed, and only brain magnetic resonance imaging showed a large cerebral hydatid cyst located within the dura layers between the periosteal and the endosteal layers. Surgery was performed without cyst rupture, confirming the intracerebral intradural location. Conclusion: Early diagnosis and treatment for intracranial hydatid cysts are crucial to prevent complications such as neurological deficits, seizures, and even death. In this case, the intracerebral intradural location of the cyst is extremely rare.

A clinical study of patients with conservatively managed extra dural hematoma at a tertiary care hospital

Background: Head injury causes accumulation of blood between the rigid skull and the outer endosteal layer of the dura mater. If the volume of extradural hematoma is less than 30 ml volume, it may not require surgery based on neurological examination. Objectives: To study the various causes, factors influencing and outcome of conservatively management in Extra Dural Hematomas. Materials and Methods: A total of 23 Extra Dural Hematoma cases requiring conservative management were included in the study. All the patients were subjected to complete neurological examination including and various imaging techniques like CT brain and chest X-ray. The patients with volume<30ml, thickness<5 mm, midline shift<5 mm, GCS >8, were subjected to conservative management by admitting the patients in Intensive Care Units (ICU). Results: Among 23 EDH cases, 17 (74%) cases were males and 6(26%) cases were females. The mean age of patients was 26.7years. Road traffic accident was the common mode of injury in 47.8% (11 cases) of patients. Mean volume of hematoma was 20.5ml and GCS Score was mild to moderate group.The majority of the patients (34.7%) presented with frontal EDH. Among 23 cases, 91.3% of the patients were discharged with good recovery. Conclusion: Extra Dural Hematoma (EDH) with low volume can be considered for conservative therapy by close observation, yet a risk of sudden neurological deterioration. However, surgical evacuation is the definitive treatment of EDH but craniotomy can be avoided in many patients with keen observation and repeated neurological assessments.

A clinical study of patients with conservatively managed extra dural hematoma at a tertiary care hospital

Background: Head injury causes accumulation of blood between the rigid skull and the outer endosteal layer of the dura mater. If the volume of extradural hematoma is less than 30 ml volume, it may not require surgery based on neurological examination. Objectives: To study the various causes, factors influencing and outcome of conservatively management in Extra Dural Hematomas. Materials and Methods: A total of 23 Extra Dural Hematoma cases requiring conservative management were included in the study. All the patients were subjected to complete neurological examination including and various imaging techniques like CT brain and chest X-ray. The patients with volume<30ml, thickness<5 mm, midline shift<5 mm, GCS >8, were subjected to conservative management by admitting the patients in Intensive Care Units (ICU). Results: Among 23 EDH cases, 17 (74%) cases were males and 6(26%) cases were females. The mean age of patients was 26.7years. Road traffic accident was the common mode of injury in 47.8% (11 cases) of patients. Mean volume of hematoma was 20.5ml and GCS Score was mild to moderate group.The majority of the patients (34.7%) presented with frontal EDH. Among 23 cases, 91.3% of the patients were discharged with good recovery. Conclusion: Extra Dural Hematoma (EDH) with low volume can be considered for conservative therapy by close observation, yet a risk of sudden neurological deterioration. However, surgical evacuation is the definitive treatment of EDH but craniotomy can be avoided in many patients with keen observation and repeated neurological assessments.

Anatomy and Histology of the Petrous Carotid Membrane: Application to Skull Base Surgery

Published reports regarding the tissue types that surround the internal carotid artery (ICA) as it travels through the carotid canal vary. Reports have variably defined this membrane as periosteum, loose areolar tissue, or dura mater. With such discrepancies and realizing that knowledge of this tissue might be important for skull base surgeons who expose or mobilize the ICA at this location, the present anatomical/histological study was performed. In 8 adult cadavers (16 sides), the contents of the carotid canal were evaluated; specifically, the membrane surrounding the petrous part of the ICA was studied, and its relationship to the deeper lying artery was observed. These specimens were stored in formalin and submitted for histological evaluation. Grossly, the membrane within the carotid canal traversed the entire carotid canal and was loosely adherent to the underlying petrous part of the ICA. Histologically, all membranes surrounding the petrous part of the ICA were consistent with dura mater. The dura mater of the carotid canal had an outer endosteal layer and an inner meningeal layer as well as a clear dural border cell layer in most specimens that approximated and was loosely applied to the adventitial layer of the petrous part of the ICA. The membrane that surrounds the petrous part of the ICA is dura mater. To our knowledge, this is the first histological investigation of this structure and thus serves to establish the true identity of this membrane and correct previous reports in the literature that have erroneously concluded that it is periosteum or loose areolar tissue.

A multi-niche microvascularized human bone marrow (hBM) on-a-chip elucidates key roles of the endosteal niche in hBM physiology

The human bone marrow (hBM) is a complex organ critical for hematopoietic and immune homeostasis, and where many cancers metastasize. Understanding the fundamental biology of the hBM in health and diseases remain difficult due to complexity of studying or manipulating the BM in humans. Accurate biomaterial-based in vitro models of the hBM microenvironment are critical to further our understanding of the BM-niche and advancing new clinical interventions. Here we report a unique, 96-well format, microfluidic hBM-on-a-chip that incorporates the endosteal, central marrow, and perivascular niches of the human BM. Osteogenic differentiation of donor human mesenchymal stromal cells (MSCs) produced robust mineralization on the bottom surface (“bone-like endosteal layer”) of the device, and subsequent seeding of human endothelial cells and MSCs in a fibrin-collagen hydrogel network (“central marrow”) on the top created an interconnected 3D microvascular network (“perivascular niche”). The 96-well format allows eight independent “chips” to be studied in one plate, thereby increasing throughput and reproducibility. We show that this complex, multi-niche microtissue accurately mimics hBM composition and microphysiology, while providing key insights on hematopoietic progenitor dynamics. Presence of the endosteal niche decreased the proliferation and increased maintenance of CD34+ hematopoietic stem cells (HSCs). Upon exposure to radiation, HSCs in the hBM-chips containing endosteal niches were less frequently apoptotic, suggesting a potentially radio-protective role of the osteoblast surface. Our methods and results provide a broad platform for creating complex, multi-niche, high-throughput microphysiological (MPS) systems. Specifically, this hBM-on-a-chip opens new opportunities in human bone marrow research and therapeutics development, and can be used to better understand normal and impaired hematopoiesis, and various hBM pathologies, including cancer and BM failures.

Cortical Bone Loss Following Gastric Bypass Surgery Is Not Primarily Endocortical.

Roux-en Y gastric bypass (RYGB) surgery is an effective treatment for obesity; however, it may negatively impact skeletal health by increasing fracture risk. This increase may be the result not only of decreased bone mineral density but also of changes in bone microstructure, for example, increased cortical porosity. Increased tibial and radial cortical porosity of patients undergoing RYGB surgery has been observed as early as 6 months postoperatively; however, local microstructural changes and associated biological mechanisms driving this increase remain unclear. To provide insight, we studied the spatial distribution of cortical porosity in 42 women and men (aged 46 ± 12 years) after RYGB surgery. Distal tibias and radii were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) preoperatively and at 12months postoperatively. Laminar analysis was used to determine cortical pore number and size within the endosteal, midcortical, and periosteal layers of the cortex. Paired t tests were used to compare baseline versus follow-up porosity parameters in each layer. Mixed models were used to compare longitudinal changes in laminar analysis outcomes between layers. We found that the midcortical (0.927 ± 0.607 mm-2 to 1.069 ± 0.654 mm-2 , p=0.004; 0.439 ± 0.293 mm-2 to 0.509 ± 0.343 mm-2 , p=0.03) and periosteal (0.642 ± 0.412 mm-2 to 0.843 ± 0.452 mm-2 , p < 0.0001; 0.171 ± 0.101 mm-2 to 0.230 ± 0.160 mm-2 , p=0.003) layers underwent the greatest increases in porosity over the 12-month period at the distal tibia and radius, respectively. The endosteal layer, which had the greatest porosity at baseline, did not undergo significant porosity increase over the same period (1.234 ± 0.402 mm-2 to 1.259 ± 0.413 mm-2 , p=0.49; 0.584 ± 0.290 mm-2 to 0.620 ± 0.299 mm-2 , p=0.35) at the distal tibia and radius, respectively. An alternative baseline-mapping approach for endosteal boundary definition confirmed that cortical bone loss was not primarily endosteal. These findings indicate that increases in cortical porosity happen in regions distant from the endosteal surface, suggesting that the underlying mechanism driving the increase in cortical porosity is not merely endosteal trabecularization. © 2022 American Society for Bone and Mineral Research (ASBMR).

Optical coherence tomography of cranial dura mater: Microstructural visualization in vivo

PurposeThe study explores microscope integrated optical coherence tomography (OCT) as a intraoperative imaging technique to delineate the microstructural composition of human dura mater cranialis and underlying leptomeninges for surgical guidance. MethodsOCT volume scans, light microscopic pictures and light microscopic videos of the dura mater were acquired in patients (n = 20) with indication for craniotomy. OCT volume scans and corresponding light microscopic data were analyzed post procedural. Thickness of anatomical structures was measured during this phase. ResultsOCT scanning of the human cranial dura mater was feasible during microsurgical dissection. A discrimination of the endosteal and inner meningeal layer of the cranial dura mater was possible in 70 % (n = 14) of the patients. Transdural OCT scans could further demonstrate subdural anatomical structures: subdural space 10 % (n = 2), subarachnoid space in 35 % (n = 7), arachnoid vessels in 80 % (n = 16) and brain cortex in 90 % (n = 16) of the patients. Orthogonal distance measurement was possible. The cranial dura mater showed a mean depth of 216 μm, the endosteal layer of 120 μm and the inner meningeal layer of 132 μm. Imaging quality of the dural segment was high – approaching spatial resolution of histopathology. Imaging quality of subdural segments was lower and demonstrated A-line artifacts in 45 % (n = 7). ConclusionThese results illustrate - for the first time - strengths and weaknesses of three dimensional microscope integrated OCT as an in vivo imaging method of the human cranial dura mater, underlying leptomeninges and human brain cortex as a surgical guidance tool. OCT imaging of the cranial dura mater showed extensive details. Transdural imaging of subdural micro anatomical structures was possible, but showed lower image quality with intermittent A-line artifacts. OCT stated the first intraoperative imaging tool to measure the depth of micro anatomical structures with a high spatial resolution of 7,5 μm.

Dosimetry of Bone-Seeking Radiopharmaceuticals for Palliative Therapy of Bone Metastases: A Simulation Study Using GATE Monte Carlo Code

Purpose: Radiopharmaceutical Therapy (RPT) is one of the effective methods for pain palliation of bone metastases. Bone marrow is a critical organ in bone structure whose absorbed dose should be kept below a certain threshold. The purpose of this study was to calculate and compare absorbed doses of bone-seeking radiopharmaceuticals used in the palliative treatment of bone metastases. Materials and Methods: In this study, the GATE Monte Carlo code was used to simulate a femur bone, which consists of bone marrow, endosteal layer, bone, and soft tissue phantom model. Absorbed doses of the 153Sm-EDTMP, 89SrCl2, 177Lu-EDTMP, 188Re-HEDP, and 223RaCl2 radiopharmaceuticals were calculated in the femur phantom compartments. Results: bone absorbed doses per disintegration from alpha particles of 223RaCl2 is approximately 24 times higher than absorbed doses from beta particles of 89SrCl2. Also, absorbed dose per disintegration from beta particles of 89SrCl2 in the bone is approximately 12, 6 and 1.5 times higher than 177Lu-EDTMP, 153Sm-EDTMP, and 188Re-HEDP, respectively. Moreover, the bone and bone marrow absorbed dose from beta particles of 153Sm-EDTMP is 1.9 times higher than 177Lu-EDTMP. Besides, absorbed dose per disintegration from beta particles of 188Re-HEDP in the bone marrow is approximately 40, 30, 7, and 4 times higher than 223RaCl2, 89SrCl2, 177Lu-EDTMP and 153Sm-EDTMP, respectively. Conclusion: Our results show that 223RaCl2 could be a more efficient radiopharmaceutical for radionuclide therapy of bone metastases. Also, 177Lu-EDTMP, due to low marrow toxicity and comparable bone absorbed dose with 153Sm-EDTMP, can be used for achieving bone pain palliation. Moreover, significantly high bone marrow absorbed dose of 188Re-HEDP should be considered for palliative therapy of metastatic bone patients.

Fine configuration of the dural fibrous network and the extradural neural axis compartment in the jugular foramen: an epoxy sheet plastination and confocal microscopy study.

The extradural neural axis compartment (EDNAC) is an adipovenous zone that is located between the meningeal (ML) and endosteal (EL) layers of the dura mater and has been minimally investigated in the jugular foramen (JF) region. In this study, the authors aimed to explore the fine architecture of the EDNAC within the JF and evaluate whether the EDNAC can be used as a component for JF compartmentalization. A total of 46 cadaveric heads (31 male, 15 female; age range 54-96 years) and 30 dry skulls were examined in this study. Twelve of 46 cadaveric heads were plastinated as a series of transverse (7 sets), coronal (3 sets), and sagittal (2 sets) slices and examined using stereomicroscopy and confocal microscopy. The dural entry points of the JF cranial nerves were recorded in 34 cadaveric skulls. The volumes of the JF, intraforaminal EDNAC, and internal jugular vein (IJV) were quantified. Based on constant osseous landmarks, the JF was subdivided into preforaminal, intraforaminal, and subforaminal segments. The ML-derived fascial sheath along the anteromedial wall of the IJV demarcated the "venous portion" and the "EDNAC portion" of the bipartite JF. The EDNAC did not surround the intraforaminal IJV and comprised an ML-derived dural fibrous network and an adipose matrix. A fibrovenous curtain subdivided the intraforaminal EDNAC into a small anterior column containing cranial nerve (CN) IX and the anterior condylar venous plexus and a large posterior adipose column containing CNs X and XI. In the intraforaminal segment, the IJV occupied a slightly larger space in the foramen (57%; p < 0.01), whereas in the subforaminal segment it occupied a space of similar size to that of the EDNAC. Excluding the IJV, the neurovascular structures in the JF traverse the dural fibrous network that is dominant in the foraminal EDNAC. The results of this study will contribute to anatomical knowledge of the obscure yet crucially important JF region, increase understanding of foraminal tumor growth and spread patterns, and facilitate the planning and execution of surgical interventions.

Morphofunctional Aspects of Bone Tissue at Osteoporosis

Objective: morphofunctional aspects of bone tissue at osteoporo-sis. Methods: The clinical material of 117 patients with isolated and multiple fractures of typical localizations on background of systemic osteoporosis as well with degenerative diseases of the musculoskele-tal system, which were presented by deforming arthrosis of hip joints of 3rd degree. The specimens of bone tissue were browsed and pho-tographed in light microscope «TOPIC-T» CETI. The specimens were fixed in standard glutaraldehyde fixative and then they were browsed in raster electron microscope «FE1 Quanta 200 3D» и «FE1 Quanta 600 FEG»( Netherlands). The processing and formation of AFM- images were conducted using software «NOVA»(NT-MDT, Russia) and «Image Analysis» (NT-MDT, Russia). Results: The decreasing of total area of bone tissue was morpholog-ical manifestation of osteoporosis. Normal bone plates in cancellous bone became thin and perforated, trabecular lattice system also be-came thinner and partially interrupted. Trabeculae became thin, distance between them increased, what led to spreading of bone marrow space. The structure of Havers canals was violated. The thinning of tissue in cancellous substance was due to transformation of endoste-al layer of cortical bone. The fibres of intercellular substance of bone tissue were placed randomly, large intervals were between bunches. Conclusions: At exploration of morphofunctional features of bone tissue at osteoporosis it was founded that the decreasing of total area of solid substance in bone tissue took place. In cancellous substance bone plates became perforated and thin, collapsed, forming large cavities. Trabecular lattice system became thin and partially interrupt-ed. Trabeculae became thin, distance between them increased.

Irregular Contour of Inner Ear Structures and Hypomineralized Areas at Otic Capsule: Are They Other Additional Imaging Findings of Incomplete Partition-III?

Incomplete partition III (IP-III) characterized by congenital mixed or sensorineural hearing loss is a rare genetic disease transmitted through X-linked inheritance. Incomplete partition III can be easily achieved based on pathognomonic computed tomography findings. The aims of this study were to investigate the otic capsule abnormalities in IP-III and to report irregular contour of membranous labyrinth and hypomineralized areas at otic capsule, which have not previously been described. The otic capsule features of 10 subjects (8 affected patients, 1 of whom is a female; 2 carrier mothers), who were diagnosed on clinical and typical radiologic findings, were analyzed. All patients had typical IP-III as described in the literature. Seven of 10 patients had irregular contour. Seven of 10 patients demonstrated hypomineralized areas, which were very hypodense to normally develop otic capsule areas. One affected patients and 2 carrier mothers had a normal-looking membranous labyrinth contour and normal mineralization at otic capsule. We report for the first time the irregular contour of inner ear structures and hypodense otic capsule areas in patients with IP-III. We think that though speculative, abnormal development of the inner endosteal layer results in irregular contour of inner ear structures. Hypomineralized areas at otic capsule could be explained by abnormal development of middle enchondral layer due to reduced or absent vascular supply from middle ear mucosa during fetal life. These findings may be accepted as additional criteria of IP-III.

Application of a Trabecular and Cellular Model of Bone Marrow Dosimetry for Targeted 223Ra Therapy

139 Objectives: Absorbed dose-based treatment planning is a desirable objective for all radiopharmaceutical therapy. Ra-223, a bone-seeking radionuclide, has been used extensively as a therapeutic for bone metastases of prostate cancer. However, dosage follows a strict regimen based on mass, due to the complexity of the dosimetry including the low count rate of emissions, the disseminated and dynamic natures of the disease and organ at risk, the multiplicity of radioactive daughters as well as the short range and high LET of the alpha-particles. We propose to take an important step in Ra-223 bone marrow dosimetry by combining (a) small scale geometrical trabecular and cellular model, (b) detailed α-particle absorbed fractions from human cadaver studies, (c) high resolution autoradiography of resected mouse femurs and (d) clinical pharmacokinetics. Methods: Human pharmacokinetics, time-integrated activity (TIA) and whole organ absorbed dose values, including blood and bone were taken from the literature. The time integrated activity (number of decays) in the bone was apportioned to the bone matrix, endosteal layer and marrows cavities based on murine imaging data obtained using high resolution storage phosphor autoradiography as well as alpha-Camera images of resected mouse femurs sectioned on a cryostat. These TIAs were converted to absorbed dose to the endosteal layer, the bone matrix and the marrow as a function of marrow distance from bone surface different depths using absorbed fractions obtained from human cadaver data from a previous publication. The trabecular and cellular model was used to obtain cell dose histograms. Results: The activity and therefore TIA was primarily concentrated in the endosteal layer. Consequently, due to the short range of the α emitters, the absorbed dose was predominantly deposited near the bone surface, either in the endosteal layer or the shallow marrow. The dose cell histograms results were used to plot the percentage of marrow cells that received less than a potentially toxic dose (2 or 4 Gy) as a function of the average absorbed dose. The results show a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity, such that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity results in only a small increase in number of marrow cell with cytotoxic dose. Conclusions: Small scale modeling has been successful at interpreting localized dose in other organs, such as the kidneys and salivary glands. The dynamic and systemic nature of the bone marrow make it a more complex organ at risk, yet the use of small scale modeling offers insight into the lack of expected bone marrow toxicity as calculated from average absorbed dose and is a significant step towards reconciling dosimetry and toxicity.

First Pterosaur Post-Cranial Remains from the Lower Cretaceous Lohan Cura Formation (Albian) of Patagonia, Argentina

In this contribution, we present the first pterosaur post-cranial bone from the Lohan Cura Formation (Albian) of the Cerro de los Leones locality (Picun Leufu, Neuquen Province). The material is an incomplete left ulna, preserved in three dimensions, and composed of the proximal epiphysis and part of the diaphysis. The element shares several affinities with derived pterodactyloid pterosaurs, such as a diaphysis with a sub-oval cross-section, thin bone walls, pneumatic foramina in the dorsal surface of the proximal epiphysis and between the cotyles, and wingspan reconstruction indicating a medium-size specimen. An analysis of the microstructure allowed us to evaluate the ontogenetic stage of the specimen. The thin-section from the mid-shaft shows a wide and sub-circular medullary cavity, encircled by a thin cortical bone ring. In the innermost cortex, secondary lamellar bone forms a distinct and avascular endosteal layer, while the cortical layer is dominated by a well vascularized primary bone with coarse parallel fibers, as in other pterodactyloids. The presence of an avascular endosteal lamellar layer, an unremodeled cortical layer dominated by parallel-fibered bone, and a well ossified proximal epiphysis suggest that the specimen was an advanced juvenile or sub-adult with active-growth at the time of death. Considering the limited pterosaurian fossil record of Argentina, the new pterosaur specimen not only contributes to the reconstruction of the paleoecosystem of the Lohan Cura Formation in the central Neuquen Basin, but also improves our knowledge on the pterosaur taxonomic diversity during the Early Cretaceous of Patagonia.

Application of a Trabecular and Cellular Model of Bone Marrow Dosimetry for Targeted 223Ra Therapy

There is growing awareness in the radiopharmaceutical therapy community that dosimetry-based treatment planning is a highly desirable objective, potentially leading to greater efficacy and safety for patients. Ra-223, a bone-seeking radionuclide, has been used extensively as a therapeutic for bone metastases of prostate cancer. However, dosage follows a strict regimen based on mass and attempts to understand the dosimetry of Ra-223 have had limited success, in part due to the low count rate of emissions, the disseminated and dynamic natures of the disease and organ at risk, the multiplicity of radioactive daughters as well as the short range and high LET of the alpha-particles, making it the most difficult dosimetry of any radiopharmaceutical to date. We propose to take the next step in Ra-223 bone marrow dosimetry by combining (a) small scale geometrical trabecular and cellular model, (b) detailed alpha-particle absorbed fractions from human cadaver studies, (c) high resolution autoradiography of resected mouse femurs and (d) clinical pharmacokinetics. Human pharmacokinetics, time-integrated activity (TIA) and whole organ absorbed dose values, including blood and bone were taken from the literature for patients treated with 100 kBq/kg. The time integrated activity (number of decays) in the bone was apportioned to the bone matrix, endosteal layer and marrows cavities based on murine imaging data obtained using high resolution storage phosphor autoradiography as well as alpha-Camera images of resected mouse femurs sectioned on a cryostat. These TIAs were converted to absorbed dose to the endosteal layer, the bone matrix and the marrow as a function of marrow distance from bone surface different depths using absorbed fractions obtained from human cadaver data from a previous publication. The trabecular and cellular model was used to obtain cell dose histograms. The activity and therefore TIA was primarily concentrated in the endosteal layer. Consequently, due to the short range of the α emitters, the absorbed dose was predominantly deposited near the bone surface, either in the endosteal layer or the shallow marrow. The dose cell histograms results were used to plot the percentage of marrow cells that received less than a potentially toxic dose (2 or 4 Gy) as a function of the average absorbed dose. The results show a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity, such that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity results in only a small increase in number of marrow cell with cytotoxic dose. Small scale modeling has been successful at interpreting localized dose in other organs, such as the kidneys and salivary glands. The dynamic and systemic nature of the bone marrow make it a more complex organ at risk, yet the use of small scale modeling offers insight into the lack of expected bone marrow toxicity as calculated from average absorbed dose and is a significant step towards reconciling dosimetry and toxicity.

Comparison between Targeted Radionuclide Therapy of Bone Metastases Based on β-Emitting and α-Emitting Radionuclides

IntroductionThe α- and β-emitter radionuclides are used for palliative treatment of bone metastasis. Our objective was to compare the dosimetric parameters of radionuclides used in bone pain palliation therapy. MethodsMonte Carlo code, MCNPX, was used to simulate radiation transport. Dosimetric calculations were performed for monoenergetic electrons with energies of 0.1–3 MeV, α-particles with energies of 3–10 MeV, and several radionuclides 32P, 89Sr, 153Sm, 177Lu, 223Ra, and its progeny. The simulated phantom consisted of bone marrow, an endosteal layer, bone, and soft tissue. Source tissues included bone marrow, endosteal layer, and bone. Absorbed fractions and specific absorbed fractions were calculated for target regions. Absorbed doses were calculated for investigated radionuclides. ResultsThe obtained results demonstrated that the dosimetric parameters vary depending on the source or target size, particle energy, and location of the source. The β-emitter radionuclides were able to penetrate the bone marrow region, whereas the α-emitter radionuclides gave a higher and localized dose to the bone and endosteal layer in comparison. Conclusion223Ra and 177Lu have fewer side effects on the bone marrow, and they may be a better choice for use in bone pain palliation radiotherapy.

Abstract 1083A: An ex vivo 3D bone metastasis model for prostate cancer

Abstract Introduction: Bone is the preferred site for prostate cancer (PCa) metastases and there is virtually no cure once the tumor is established within this niche. The development of therapeutic strategies against metastatic PCa has been limited by the lack of an all-human preclinical model to: (1) study PCa-bone interactions under physiologically relevant three dimensional (3D) microenvironments, (2) understand how these interactions result in the development of drug resistance, and (3) explore paradigm-changing precision medicine concepts. Methods: Conditionally reprogrammed primary PCa cells (CR-PCa, derived from a lymph node metastatic site) were integrated with our ex vivo human 3D bone tissue platform, as a transformative approach for modeling tumor behavior at the bone niche. The 3D bone tissue was engineered using primary osteoblastic (OSB) cells from human bone samples. These cells were biomimetically assembly with biphasic calcium phosphate microbeads (BCPm) in perfusion microfluidic culture devices. BCPm were used to replicate the 3D cellular network of OSTs in human bone. This 3D tissue model was successfully used to support the osteocytic differentiation of primary human OSB cells within the BCPm structure, while maintaining a single cell layer of osteoblasts on the surface of the 3D tissue resembling the bone endosteum. Results: Integration of the 3D bone tissue with CR-PCa cells resulted in a compromised endosteal layer after only 4 days of coculture, with more apoptotic OSTs in the tissues with CR-PCa vs. no PCa cells controls (P&amp;lt;0.01). For functional analysis, we stained 5 μm sections of the 3D tissues for alkaline phosphatase (ALP, an OSB marker) and sclerostin, an osteocytic marker and major signaling molecule released by embedded OSTs that suppresses osteoblastogenesis. Quantification of immunofluorescence staining revealed that ALP was significantly increased (P&amp;lt;0.05), whereas sclerostin significantly decreased (P&amp;lt;0.01) with the introduction of CR-PCa cells. This OSB phenotype, induced by PCa-bone interactions ex vivo, is entirely consistent with the OSB prostate cancer-bone metastasis niche seen in patients with advanced disease. Conclusions: Our model recapitulates: (1) an OSB monolayer closely resembling the endosteum at the bone/ bone marrow interface, (2) the complex microphysiological features and functions of 3D-networked OSTs, and (3) the interactions of primary PCa cells with osteoblasts and OSTs. Citation Format: Jenny Zilberberg, Saba Choudhary, Eugenia Dziopa, Cirian Mannion, Yair Kissin, Erika Parasido, Christopher Albanese, Woo Lee. An ex vivo 3D bone metastasis model for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1083A.

Evidence of Osteoclastic Activity in the Human Temporal Bone

Bone remodeling within the otic capsule has been reported to be inhibited especially at or near the cochlea, except under some pathological conditions such as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur. Microcavitations found in periosteal and endosteal layers of human temporal bone specimens without otosclerosis, Paget's disease, or inflammation as reported in the current study are consistent with osteoclastic bone resorption. Thirty-three temporal bones from 33 patients were prepared for light microscopy and classified into 4 groups: histologically proven dehiscence of the superior semicircular canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older and with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic locations in the temporal bone in all 4 groups, but not in the cochlea or vestibule. Microcavitation within the temporal bone is likely due to osteoclastic activity, and it is seen in both young and old patients, patients with and without otosclerosis, and in cases with SSCD.

The interperiosteodural concept applied to the jugular foramen and its compartmentalization.

OBJECTIVE The dura mater is made of 2 layers: the endosteal layer (outer layer), which is firmly attached to the bone, and the meningeal layer (inner layer), which directly covers the brain and spinal cord. These 2 dural layers join together in most parts of the skull base and cranial convexity, and separate into the orbital and perisellar compartments or into the spinal epidural space to form the extradural neural axis compartment (EDNAC). The EDNAC contains fat and/or venous blood. The aim of this dissection study was to anatomically verify the concept of the EDNAC by focusing on the dural layers surrounding the jugular foramen area. METHODS The authors injected 10 cadaveric heads (20 jugular foramina) with colored latex and fixed them in formalin. The brainstem and cerebellum of 7 specimens were cautiously removed to allow a superior approach to the jugular foramen. Special attention was paid to the meningeal architecture of the jugular foramen, the petrosal inferior sinus and its venous confluence with the sigmoid sinus, and the glossopharyngeal, vagus, and accessory nerves. The 3 remaining heads were bleached with a 20% hydrogen peroxide solution. This procedure produced softening of the bone without modifying the fixed soft tissues, thus permitting coronal and axial dissections. RESULTS The EDNAC of the jugular foramen was limited by the endosteal and meningeal layers and contained venous blood. These 2 dural layers joined together at the level of the petrous and occipital bones and separated at the inferior petrosal sinus and the sigmoid sinus, and around the lower cranial nerves, to form the EDNAC. Study of the dural sheaths allowed the authors to describe an original compartmentalization of the jugular foramen in 3 parts: 2 neural compartments-glossopharyngeal and vagal-and the interperiosteodural compartment. CONCLUSIONS In this dissection study, the existence of the EDNAC concept in the jugular foramen was demonstrated, leading to the proposal of a novel 3-part compartmentalization, challenging the classical 2-part compartmentalization, of the jugular foramen.

Spectral K-edge subtraction imaging of experimental non-radioactive barium uptake in bone

PurposeTo evaluate the feasibility of using non-radioactive barium as a bone tracer for detection with synchrotron spectral K-edge subtraction (SKES) technique. MethodsMale rats of 1-month old (i.e., developing skeleton) and 8-month old (i.e., skeletally mature) were orally dosed with low dose of barium chloride (33mg/kg/day Ba2+) for 4weeks. The fore and hind limbs were dissected for imaging in projection and computed tomography modes at 100μm and 52μm pixel sizes. The SKES method utilizes a single bent Laue monochromator to prepare a 550eV energy spectrum to encompass the K-edge of barium (37.441keV), for collecting both ‘above’ and ‘below’ the K-edge data sets in a single scan. ResultsThe SKES has a very good focal size, thus limits the ‘crossover’ and motion artifacts. In juvenile rats, barium was mostly incorporated in the areas of high bone turnover such as at the growth plate and the trabecular surfaces, but also in the cortical bone as the animals were growing at the time of tracer administration. However, the adults incorporated approximately half the concentration and mainly in the areas where bone remodeling was predominant and occasionally in the periosteal and endosteal layers of the diaphyseal cortical bone. ConclusionsThe presented methodology is simple to implement and provides both structural and functional information, after labeling with barium, on bone micro-architecture and thus has great potential for in vivo imaging of pre-clinical animal models of musculoskeletal diseases to better understand their mechanisms and to evaluate the efficacy of pharmaceuticals.