Adjacent Parenchyma Research Articles

PcWRKY1 Represses Transcription of Yellow Stripe-Like 3 (PcYSL3) to Negatively Regulate Radial Cadmium Transport in Poplar Stems.

A considerable amount of cadmium (Cd) can accumulate in the bark of poplar stems, but the Cd transport pathway and its underlying molecular mechanisms remain unknown. Here, a Cd radial transport pathway in poplar stems and a previously unrecognized PcWRKY1-Yellow Stripe-Like 3 (PcYSL3) module that regulates Cd transport are identified in Populus × canescens (Aiton) Sm. Cadmiun-nicotianamine (Cd-NA) in xylem vessels in poplar stem-wood is unloaded to adjacent ray parenchyma cells and further radially transported to bark-phloem. PcYSL3 is putatively identified as involved in Cd radial transport in poplar stems. PcYSL3 is highly expressed in ray parenchyma cells adjacent to xylem vessels and the encoded protein localizes on the plasma membrane. Cd accumulation is greater in the wood and bark of PcYSL3-overexpressing poplars than the wild type, whereas the opposite is observed in PcYSL3-knockdown plants. PcWRKY1 can bind to the PcYSL3 promoter sequence and represses its expression. PcWRKY1 inhibits Cd accumulation in the wood and bark of plants. Thus, PcWRKY1 suppresses PcYSL3 transcription to negatively regulate Cd-NA unloading from xylem vessels to adjacent ray parenchyma cells and its radial transport in poplar stem. The findings have provided new insights into breeding of poplars for more effective remediation of heavy metal-contaminated soils.

ANGI-08. SPATIAL TRANSCRIPTOMIC COMPARISONS OF GLIOBLASTOMA TISSUE REVEAL UPREGULATION OF NEURODEVELOPMENTAL PATHWAYS AND SYNAPTIC GENES IN INFILTRATING TUMOR CELLS

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, chemotherapy, and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Gene expression profiling allows glioblastoma tumor cores to be classified into mesenchymal, proneural, and classical subtypes, each with distinct genetic alterations and cellular compositions. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using single-cell and multicellular resolution spatial transcriptomics on tissues from both the tumor core and infiltrated brain tissue (n = 11), we compared the transcriptional profiles of malignant cells in these regions. Malignant cells near regions with microvascular proliferation showed increased expression of genes related to vascular homeostasis. Within tumor cores, proneural and mesenchymal subtypes exhibited distinct spatial gene expression patterns, although these differences were reduced in the infiltrated brain tissue, apart from gene expression due to chromosomal alterations specific to the proneural subtype. We identified two transcriptional patterns of brain infiltration, with the dominant pattern showing a transition from mesenchymal to proneural states. This transition was accompanied by increased expression of genes linked to neurodevelopmental pathways and glial cell differentiation. Additionally, one gene module upregulated in infiltrating malignant cells was predictive of poor patient survival and enriched for genes associated with differentiated neuronal cells. Together, our findings provide an updated view of the spatial landscape of glioblastomas and infiltrated brain tissue, furthering our understanding of the malignant cells that invade healthy brain. This insight offers new avenues for targeted therapy after surgical resection of the primary tumor.

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma.

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Tubercular Osteomyelitis of Skull: Case Report and Review of the literature

Skeletal tuberculosis constitutes about 1j of all cases. Usually, spine and limb bones are involved. Tubercular osteomyelitis of the skull is a rare entity; therefore, diagnosis is rarely suspected. We report one such rare case of an atypical calvaria skull osteomyelitis in a14 years old female who presented with swelling on the right frontoparietal region for 3 months. CT scan of brain and bony window revealed a lytic bony lesion at the right parietal bone with associated epidural soft tissue component at the right parietal top causing compression over adjacent parenchyma- possibly eosinophilic granuloma or chronic osteomyelitis. Patient was treated surgically by excision of the lesion with cranioplasty by synthetic bone cement. After surgical treatment, the specimen was sent for histopathology which showed granulomatous inflammation histologically consistent with tuberculosis. She was treated with antitubercular therapy. Our Case highlights all these aspects of skull tuberculosis with review of the available literature relevant to skull tubercular osteomyelitis. EWMCJ Vol. 12, No. 1&2, January-July 2024: 111-119

A brain-wide solute transport model of the glymphatic system.

Brain waste is largely cleared via diffusion and advection in cerebrospinal fluid (CSF). CSF flows through a pathway referred to as the glymphatic system, which is also being targeted for delivering drugs to the brain. Despite the importance of solute transport, no brain-wide models for predicting clearance and delivery through perivascular pathways and adjacent parenchyma existed. We devised such a model by upgrading an existing model of CSF flow in the mouse brain to additionally solve advection-diffusion equations, thereby estimating solute transport. We simulated steady-state transport of 3 kDa dextran injected proximal to the perivascular space (PVS) of the middle cerebral artery, mimicking in vivo experiments. We performed a sensitivity analysis of 11 biological properties of PVSs and brain parenchyma by repeatedly simulating solute transport with varying parameter values. Parameter combinations that led to a large total pressure gradient, poor CSF perfusion or a steep solute gradient were deemed unrealistic. Solute concentrations in parenchyma were most sensitive to changes in pial PVS size, as this parameter linearly affects volume flow rates. We also found that realistic transport requires both highly permeable penetrating PVSs and high-resistance parenchyma. This study highlights the potential of brain-wide models to provide insights into solute transport processes.

Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue

Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection.

Intraoperative Comparison Between Strain Elastography and Preoperative Magnetic Resonance Imaging Features in High-Grade Gliomas Using Fusion Imaging: A Pilot Study

To compare the elastographic patterns of high-grade gliomas (HGGs) solid portions and those of adjacent healthy brain parenchyma, on intraoperative ultrasound, with magnetic resonance image (MRI) characteristics. Clinical records and images of HGGs patients, operated between June and December 2018, were retrospectively reviewed. Fusion images were used to compare preoperative gadolinium-enhanced T1-weighted MRI/fluid-attenuated inversion recovery images (Gd-T1 MRI/FLAIR) to intraoperative strain elastography (SE). FLAIR/Gd-T1 MRI images were used to define: enhancement patterns (absent/whole lesion/peripheral) and lesions' characteristics (primary and secondary pattern, further subdivided in solid/necrotic/cystic/infiltrating). HGGs SE patterns were categorized as homogeneous/inhomogeneous, while lesions' primary and secondary patterns as stiff/intermediate/elastic. The SE motive of neighboring healthy brain parenchyma was defined similarly. 18 patients (M:F, 11:7; mean age: 53 years) harboring 14 glioblastomas (77.8%, GBMs) and 4 anaplastic astrocytomas (22.2%, AAs) were compared. GBMs typically enhanced peripherally and had a primary necrotic pattern (78.6% and 64.3%, respectively), while AAs did not enhance and were solid (75% both) at T1-Gd MRI and FLAIR images. At SE AAs had a homogeneous stiff primary pattern, whereas the majority of GBMs primary patterns were heterogeneous (85.7%) and intermediate (78.6%). Three major SE patterns defined HGGs and adjacent healthy brain parenchyma. SE patterns varied accordingly to HGG histotypes and Gd-T1 MRI/FLAIR characteristics.

AB025. Efficacy of 5-ALA brightness analysis for malignant brain tumor surgery.

For fluorescence-guided neurosurgery, 5-aminolevulinic acid (5-ALA) is widely used for intraoperative tumor visualization. We quantified the brightness of 5-ALA by Image J and report the pathological results of glioma, and non-tumor lesions. From 2019 to 2023, we investigated 27 high-grade glioma patients who underwent surgery with 5-ALA. Twenty-three cases of glioblastoma (GBM) and four cases of anaplastic astrocytoma (AA) were examined. The pathological diagnosis was based on the classification of World Health Organization (WHO) 2016. The 5-ALA was administered before surgery, and the 5-ALA brightness was quantified. Other than high-grade glioma, four low-grade gliomas (LGGs), two radiation necrosis, and one inflammation patients were evaluated by Image J. In GBM, the mean brightness was 134.5±65.4, except for one negative case. AA showed the mean brightness with 180.5±51.6. All LGGs showed negative in the brightness. In two radiation necrosis cases, the mean brightness was 139.5±37.4. In one inflammatory case, the brightness was 239, but after the lesion removed, the adjacent brain parenchyma showed bright, and the border was not clear. In one GBM case, the ventricle was opened, and the brightness difference between the tumor and the ventricular wall was observed. 5-ALA brightness analysis by Image J would be helpful to distinguish between malignant glioma and LGG, and other non-tumor lesions to support rapid pathological diagnosis. Also, it would be useful to distinguish between the tumor and the ventricle wall. As for radiation necrosis and inflammation, border of the lesion is unclear.

Capillary connections between sensory circumventricular organs and adjacent parenchyma enable local volume transmission.

Among contributors to diffusible signaling are portal systems which join two capillary beds through connecting veins (Dorland 2020). Portal systems allow diffusible signals to be transported in high concentrations directly from one capillary bed to the other without dilution in the systemic circulation. Two portal systems have been identified in the brain. The first was discovered almost a century ago and connects the median eminence to the anterior pituitary gland (Popa & Fielding 1930). The second was discovered a few years ago, and links the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, a sensory circumventricular organ (CVO) (Yao et al. 2021). Sensory CVOs bear neuronal receptors for sensing signals in the fluid milieu (McKinley et al. 2003). They line the surface of brain ventricles and bear fenestrated capillaries, thereby lacking blood brain barriers. It is not known whether the other sensory CVOs, namely the subfornical organ (SFO), and area postrema (AP) form portal neurovascular connections with nearby parenchymal tissue. This has been difficult to establish as the structures lie at the midline and protrude into the ventricular space. To preserve the integrity of the vasculature of CVOs and their adjacent neuropil, we combined iDISCO clearing and light-sheet microscopy to acquire volumetric images of blood vessels. The results indicate that there is a portal pathway linking the capillary vessels of the SFO and the posterior septal nuclei, namely the septofimbrial nucleus and the triangular nucleus of the septum. Unlike the latter arrangement, the AP and the nucleus of the solitary tract share their capillary beds. Taken together, the results reveal that all three sensory circumventricular organs bear specialized capillary connections to adjacent neuropil, providing a direct route for diffusible signals to travel from their source to their targets.

Fluorescence-Guided Surgical Techniques in Adult Diffuse Low-Grade Gliomas: State-of-the-Art and Emerging Techniques: A Systematic Review.

Diffuse low-grade gliomas are infiltrative tumors whose margins are not distinguishable from the adjacent healthy brain parenchyma. The aim was to precisely examine the results provided by the intraoperative use of macroscopic fluorescence in diffuse low-grade gliomas and to describe the new fluorescence-based techniques capable of guiding the resection of low-grade gliomas. Only about 20% and 50% of low-grade gliomas are macroscopically fluorescent after 5-amino-levulinic acid (5-ALA) or fluorescein sodium intake, respectively. However, 5-ALA is helpful for detecting anaplastic foci, and thus choosing the best biopsy targets in diffuse gliomas. Spectroscopic detection of 5-ALA-induced fluorescence can detect very low and non-macroscopically visible concentrations of protoporphyrin IX, a 5-ALA metabolite, and, consequently, has excellent performances for the detection of low-grade gliomas. Moreover, these tumors have a specific spectroscopic signature with two fluorescence emission peaks, which is useful for distinguishing them not only from healthy brain but also from high-grade gliomas. Confocal laser endomicroscopy can generate intraoperative optic biopsies, but its sensitivity remains limited. In the future, the coupled measurement of autofluorescence and induced fluorescence, and the introduction of fluorescence detection technologies providing a wider field of view could result in the development of operator-friendly tools implementable in the operative routine.

MRI manifestations of 40 cases with the hepatic epithelioid hemangioendothelioma classification based on the morphology and size

Objective: To explore the MRI characteristics of the hepatic epithelioid hemangioendothelioma (HEHE) classification according to morphology and size. Methods: The clinical, pathological, and MRI imaging data of 40 cases with HEHE confirmed pathologically from December 2009 to September 2021 were retrospectively analyzed. A paired sample t-test was used for comparison between the two groups. Results: There were 40 cases (5 solitary, 24 multifocal, 9 local fusion, and 2 diffuse fusion) and 214 lesions (163 nodules, 31 masses, and 20 fusion foci). The most common features of lesions were subcapsular growth and capsular depression. The signal intensity of lesions ≤1cm was usually uniform with whole or ring enhancement. Nodules and mass-like lesions ≥1cm on a T1-weighted image had slightly reduced signal intensity or manifested as a halo sign. Target signs on a T2-weighted image were characterized by: target or centripetal enhancement; fusion-type lesions; irregular growth and hepatic capsular retraction, with ring or target-like enhancement in the early stage of fusion and patchy irregular enhancement in the late stage; blood vessels traversing or accompanied by malformed blood vessels; focal bleeding; an increasing proportion of extrahepatic metastases and abnormal liver function with the type of classified manifestation; primarily portal vein branches traversing; and reduced overall intralesional bleeding rate (17%). Lollipop signs were presented in 19 cases, with a high expression rate in mass-type lesions (42%). The fusion lesions were expressed, but the morphological manifestation was atypical. The diffusion-weighted imaging mostly showed high signal or target-like high signal. An average apparent diffusion coefficient of lesions was (1.56±0.36) ×10(-3)mm(2)/s, which was statistically significantly different compared with that of adjacent normal liver parenchyma (t=8.28, P<0.001). Conclusion: The MRI manifestations for the HEHE classification are closely related to the morphology and size of the lesions and have certain differences and characteristics that are helpful for the diagnosis of the disease when combined with clinical and laboratory examinations.

Imaging features of perinephric myxoid pseudotumors of fat.

Retrospectively evaluate multimodality imaging features of perinephric myxoid pseudotumor of fat (PMPTF). Institutional cases of PMPTF with CT, MRI and/or ultrasound evaluation from 1/1/2020 to 9/1/2023 were retrospectively reviewed. Patient demographics and clinical history were reviewed, and imaging features recorded. 14 patients with pathologically-proven PMPTF were identified (11M, 3 F; mean age 66.7 ± 17.0years; range 40-87years). Three patients (18%) had bilateral lesions; a total of 17 PMPTFs were reviewed. 15/17 (88%) were biopsy-proven; two cases were diagnosed by imaging only in patients with a contralateral biopsy-proven PMPTF. All evaluable specimens were negative for MDM2 amplification. 11/17 (65%) occurred in patients with renal disease, including 4/17 (24%) in patients with renal transplant. 100% (17/17) had CT, 11/17 (65%) MRI, and 6/17 (35%) ultrasound. The mean largest lesion dimension was 10.9 ± 4.6cm (range 4.3-17.0cm). Of cases involving native kidneys, 7/13 (54%) presented as multifocal perinephric masses and 5/13 (38%) as a solitary perinephric mass. All four transplant cases presented as infiltrative-appearing masses involving the renal sinus with lesser perinephric involvement. 14/17 (82%) lesions contained macroscopic fat on CT and MRI and 3/17 (18%) showed no macroscopic fat, all involving renal transplants. All cases with MRI demonstrated T2 hyperintensity with signal dropout on opposed-phase imaging. 11/13 (85%) PMPTF showed no or equivocal CT enhancement. Enhancement was better seen on MRI in all cases evaluated by both CT and MRI. Of the six PMPTFs imaged by ultrasound, four (67%) were heterogeneously hypoechoic and two (33%) had mixed regions of hypo-, iso- and hyperechogenicity relative to adjacent renal parenchyma. PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

Fat-Poor Hepatic Angiomyolipoma in Noncirrhotic Livers: Imaging Features, Pathology, and Differential Diagnosis.

To investigate imaging features of fat-poor hepatic angiomyolipomas in noncirrhotic livers in order to enhance the diagnostic accuracy for this condition. The clinical and imaging data of 19 patients with fat-poor hepatic angiomyolipoma (fpHAML) was retrospectively analyzed. Of the 19 patients without hepatitis, cirrhosis, or sarcoidosis, 16 had no clinical symptoms. There were 20 lesions in 19 patients. Macroscopic fat, calcification, hemorrhage, necrosis, and pseudocapsule were not observed in the 20 lesions. All lesions showed marked enhancement on the arterial phase, and the degree of enhancement was significantly higher than that in the adjacent hepatic parenchyma. In 8 cases, the enhancement of the portal phase was higher than that in the arterial phase. Multiple intratumor vessels were observed in the tumor, and lesions with diameters larger than 3.0 cm were more frequently observed. The degree of enhancement of 18 lesions on portal phase or delayed phase was slightly higher than or equal to that in the surrounding hepatic parenchyma. The lesions were hyperintense on diffusion-weighted imaging and showed homogeneous hypointensity on the hepatobiliary phase. Only 6 cases showed the presence of an early draining vein. These imaging features have some implications for the diagnosis of fpHAML. Therefore, an increased awareness of fpHAML is needed among radiologists.

Low-grade oncocytic tumor: a review of radiologic and clinical features.

The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities; one of the latter is the low-grade oncocytic tumor (LOT). This study reports the radiologic appearance and clinical behavior of LOT. In this IRB-approved, HIPPA-compliant retrospective study, our institution's pathology database was searched for low-grade oncocytic tumors or neoplasms. Patient age, gender, and comorbidities were obtained from a review of electronic medical records, and imaging characteristics of the tumors were assessed through an imaging platform. The pathology database search yielded 14 tumors in 14 patients. Four patients were excluded, as radiologic images were not available in three, and one did not fulfill diagnostic criteria after pathology re-review. The resulting cohort consisted of 10 tumors (median diameter 2.3cm, range 0.7-5.1) in 10 patients (median age 68years, range 53-91, six women). All tumors presented as a solitary, well-circumscribed, mass with solid components. All enhanced as much or almost as much as adjacent renal parenchyma; all but one enhanced heterogeneously. None had lymphadenopathy, venous invasion, or metastatic disease at presentation or at clinical follow-up (median, 22.2months, range 3.4-71.6). Among five tumors undergoing active surveillance, mean increase in size was 0.4cm/year at imaging follow-up (median 16.7months, range 8.9-25.4). LOT, a recently described pathologic entity in the kidney, can be considered in the differential diagnosis of an avidly and typically heterogeneously enhancing solid renal mass in an adult patient.

Silver Lining in the Dark Clouds: Radiological Resolution of Non-Functional Giant Pituitary Adenoma after Traumatic Spinal Cord Injury

Tumors of pituitary are considered relatively rare. Giant adenomas of this gland further add in rarity. Pituitary apoplexy (PA) is an unusual event, which may occur as a result of hemorrhage, necrosis and/or infarction within the tumor and/or adjacent gland parenchyma. The presentation of PA is highly variable. In some cases, it may be the initial presentation of tumor while at the other end of spectrum it can be asymptomatic. Whenever symptomatic, it represents medical emergency due to associated potentially lethal adrenal insufficiency and threat to permanent visual loss. Management begins with fluid resuscitation and empiric corticosteroid administration. It is followed by detailed endocrine assessment and needful supplementation. Neurosurgical decompression is indicated in a specific subset of patients. Head injury is an established factor in causation of PA, but there are only handful of cases where traumatic spinal cord injury had led to it. Cases of apoplexy culminating into resolution of adenoma are very sparse. Hereby authors report a case where non-functional giant pituitary adenoma (NFGPA) has radiologically evanished after spinal cord trauma. In this manuscript, authors also discuss the pathophysiology of apoplexy in pituitary adenomas, types of apoplexy as well as standard protocol recommended for follow-up of such cases.

NEAR-INFRARED SPECTROSCOPY IN VIVO DISTINGUISHES AMYLOID DEPOSITION IN SUBJECTS WITH ALZHEIMER’S DISEASE

Abstract Cerebral amyloid angiopathy (CAA), a condition characterized by amyloid beta peptide deposition in cerebral vasculature, is commonly found in patients with Alzheimer’s disease (AD). Previous studies have shown that it is possible to distinguish subjects with Alzheimer’s disease from age-matched controls in vivo using near-infrared (NIR) spectroscopy. However, correlating neuropathological findings with the spectral features that best distinguish disease from control remains a challenge. Tissue optics predict that pathology in the leptomeningeal vasculature should be distinguishable from that of the adjacent brain parenchyma. In this study, NIR spectra were acquired in vivo from subjects with autopsy confirmed AD (n= 26). Postmortem specimens were histologically classified according to the degree of CAA (0 to 3+) noted in the leptomeningeal vasculature for each patient. A feature selection approach was used to discover spectral features that distinguished patients with high versus minimal degrees of CAA found at autopsy (scored as 3+ vs. 0, respectively). Two distinct spectral regions around 768nm and 891nm were identified as discriminants which could properly classify patients according to their CAA score, suggesting that these regions are correlated with amyloid beta peptide deposition. These results suggest that NIR spectroscopy can be used to detect and possibly inform the burden of amyloid deposition. More research is needed to establish if this technique can be used to monitor disease progression and response to therapeutic interventions, especially in light of emerging new immunotherapies.

Analysis of MRI features of hepatocyte nuclear factor 1α-inactivated hepatocellular adenoma

Objective: To investigate the MRI imaging features of hepatocyte nuclear factor 1α- inactivated hepatocellular adenoma (H-HCA). Methods: Clinical data and MRI images of 19 H-HCA cases who were pathologically confirmed at Zhongshan Hospital Affiliated to Fudan University between August 2014 and July 2020 were retrospectively analyzed. Among them, there were 15 females and 4 males, aged 16-47 (32± 7) years old. Tumor number, location, shape, size, boundary, MRI plain scan signal intensity, dynamic enhancement features of each phase, presence or absence of intratumoral fat content, pseudocapsule, and others were analyzed. The differences in apparent diffusion coefficient (ADC) values between the lesion and the surrounding normal liver parenchyma were compared for statistical significance. t-test was used for statistical analysis. Results: There were a total of 24 lesions in 19 cases. 14 cases had solitary lesions, and five cases had multiple lesions. 15 and nine lesions were located in the right and left lobes of the liver, respectively. 20 lesions were round or quasi-round, and four were irregular or lobulated. The tumor's maximal diameter was 0.6-8.6 (3.5 ± 2.4) cm. T(1)-weighted image (WI) showed hyperintense to iso-intense signals in 20 lesions and hypointense signals in four. T(2)WI showed iso-to-slightly high signal intensity in 16 lesions, with two hyperintense and six hypointense signals. Diffusion-weighted image (DWI) revealed hyperintense to iso-intense signals. Lesions mean ADC value was (1.289 ± 0.222)×10(-3) mm(2)/s, while the adjacent normal liver parenchyma's mean ADC value was (1.307 ± 0.236)×10(-3) mm(2)/s, with no statistically significant difference between the two (P > 0.05). During the arterial phase, 15 of the 18 lesions that underwent dynamic contrast-enhanced scanning with gadoxetate disodium (Gd-DTPA) were mildly to moderately enhanced and three were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the delayed phase showed a hypointense signal. During the arterial phase, two of the six lesions scanned by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ((Gd-EOB-DTPA) dynamic enhancement were mildly to moderately enhanced, while four were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the transition and hepatobiliary-specific phases showed hypointense signals. Intracellular steatosis occurred in 21 lesions, of which 19 were diffuse steatosis and 16 formed pseudocapsules in the delayed phase. Conclusion: H-HCA often occurs in young females as solitary lesions and has certain MRI features. T1WI anti-phase diffuse signal reduction and post-enhanced hypovascular withdrawal enhancement patterns can aid in accurately diagnosing the disease condition.

Proposal for a new morphological "combined type" of gallbladder cancer: description of radiopathological characteristics and comparison with other morphological types.

To describe the radiopathological characteristics of a new morphological "combined type" of gallbladder cancer (GBC) and compare it with the mass replacing gallbladder and thickening types of GBC. The imaging and pathological details of consecutive patients with GBC between August 2020 and December 2022 were retrospectively reviewed. Two radiologists reviewed computed tomography/magnetic resonance imaging in consensus for the morphological type of GBC. The radiologists classified GBC as mass replacing gallbladder, wall thickening, and combined type. The combined type was defined as a mass arising from the thickened wall of an adequately distended gallbladder that extended exophytically into the adjacent liver parenchyma. The presence of calculi, site, and size of lesion, biliary/portal vein involvement, liver, lymph node, and omental metastases was compared among the various types. The pathological characteristics were also compared. Of the 481 patients (median age 55 years, 63.2% females) included in the study, mass replacing gallbladder, wall thickening, and combined-type GBC were seen in 42.8% (206/481), 40.5% (195/481), and 16.6% (80/481) of patients, respectively. In the combined type of GBC, biliary/portal vein involvement was seen in 63.7% (51/80) and 7.5% (6/80) of patients. Liver, lymph node, and omental metastases were seen in 67.5% (54/80), 40% (32/80), and 41.2% (33/80) patients, respectively. Liver metastases were significantly more common in the combined type (p=0.002). There were no significant differences in pathological characteristics among the various types. Combined-type GBC is less common than the mass replacing gallbladder and thickening types and is associated with a higher risk of liver metastases.

EXTH-25. IN VIVO TWO-PHOTON TUMOR IMAGING IN AN ORTHOTOPIC MEDULLOBLASTOMA MOUSE MODEL

Abstract BACKGROUND Medulloblastoma represents the most common primary brain malignancy in pediatric patients and is associated with neuro-cognitive impairment and frequent relapses after aggressive multimodal therapy. Adoptive immunotherapies such as CAR T-cell therapy are currently being investigated, showing promising results in preclinical models but lacking efficacy in first-in-human trials. Refined in vivo models to investigate reasons for treatment failures are therefore urgently needed. METHODS We developed a xenogeneic orthotopic medulloblastoma (MB) model in mice by combining a chronic cerebellar window with repetitive intravital two-photon laser scanning microscopy. Red tdTomato-fluorescent DAOY (SHH MB) tumor cells expressing B7-H3 were implanted intracranially into the cerebellum of immunodeficient mice (n = 7), and tumor cell formation was followed by in vivo-microscopy. Intravenous fluorescein isothiocyanate (FITC)-dextran was used for intravascular plasma staining. B7-H3-directed CAR T-cells were injected into the adjacent brain parenchyma. RESULTS Chronic cranial window implantation was well tolerated and allowed repetitive visualization of the mouse cerebellum. After intracranial tumor cell implantation, continuous tumor growth could be evaluated with epifluorescence as well as 2-photon laser scanning microscopy. Tumor formation was identified as early as day 5 in every mouse and could continuously be followed up to 35 days until mice succumbed due to tumor burden. Window quality and fluorescence intensity remained high until the end of the experiments. Studies on GFP-expressing CAR T-cell injection directed against B7-H3 are currently ongoing. CONCLUSIONS We herein establish a robust orthotopic medulloblastoma mouse model that allows repetitive in vivo tracking of fluorescence-expressing tumor cells, CAR T-cells and blood vessels over weeks. Such models may be used to study medulloblastoma tumor growth under the influence of different immunotherapies and reveal interactions between tumor cells and CAR T-cell therapies on a single-cell level.