Brain Tumor Imaging without Gadolinium-based Contrast Agents: Feasible or Fantasy?

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature.

The Brain Tumor Segmentation (BraTS) Challenge 2023: Glioma Segmentation in Sub-Saharan Africa Patient Population (BraTS-Africa).

Gliomas are the most common type of primary brain tumors. Although gliomas are relatively rare, they are among the deadliest types of cancer, with a survival rate of less than 2 years after diagnosis. Gliomas are challenging to diagnose, hard to treat and inherently resistant to conventional therapy. Years of extensive research to improve diagnosis and treatment of gliomas have decreased mortality rates across the Global North, while chances of survival among individuals in low- and middle-income countries (LMICs) remain unchanged and are significantly worse in Sub-Saharan Africa (SSA) populations. Long-term survival with glioma is associated with the identification of appropriate pathological features on brain MRI and confirmation by histopathology. Since 2012, the Brain Tumor Segmentation (BraTS) Challenge have evaluated state-of-the-art machine learning methods to detect, characterize, and classify gliomas. However, it is unclear if the state-of-the-art methods can be widely implemented in SSA given the extensive use of lower-quality MRI technology, which produces poor image contrast and resolution and more importantly, the propensity for late presentation of disease at advanced stages as well as the unique characteristics of gliomas in SSA (i.e., suspected higher rates of gliomatosis cerebri). Thus, the BraTS-Africa Challenge provides a unique opportunity to include brain MRI glioma cases from SSA in global efforts through the BraTS Challenge to develop and evaluate computer-aided-diagnostic (CAD) methods for the detection and characterization of glioma in resource-limited settings, where the potential for CAD tools to transform healthcare are more likely.

A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts.

BACKGROUND: The small bioactive lipid lysophosphatidic acid (LPA) plays critical roles in both normal physiology and inflammation in many systems. However, its actions are just beginning to be defined in oral biology and pathophysiology. METHODS: Microarray analysis was used to test the hypothesis that human gingival fibroblasts (GFs) would show significant changes in wound-healing and inflammation-related gene transcripts in response to a major human salivary and gingival crevicular fluid LPA species, 18:1, and that they would express transcript for the major LPA-producing enzyme autotaxin. The microarray results were validated for three highly relevant upregulated inflammatory transcripts using quantitative reverse transcription-polymerase chain reaction (QRT-PCR). Liquid chromatography-tandem mass spectrometry was used to assay time-dependent LPA species production by GFs. RESULTS: LPA 18:1 significantly regulated 20 GF novel and 27 known genes linked to the control of inflammation (P ≤0.01). QRT-PCR validation of interleukin (IL)-8, IL-11, and suppressor of cytokine signaling 2 (SOCS2) messenger RNAs confirmed statistically significant differences from control (P ≤0.05). Autotaxin transcript was present, and GFs were found to produce multiple LPA species in a time-dependent manner. CONCLUSIONS: The upregulation of transcripts for known GF proinflammatory (IL-6, IL-8) and anti-inflammatory (IL-11) ILs, along with SOCS2, shows that LPA transiently regulates a complex set of GF genes critical to periodontal wound healing and inflammation. These results implicate LPA exerting actions on GFs that are compatible with functioning as a mediator in oral fibroblast biology and inflammatory responses. Therefore, LPA may potentially modulate/regulate periodontal inflammation.

Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts.

The pleiotropic, bioactive lipid lysophosphatidic acid [(LPA), 1-acyl-sn-glycerol-3-phosphate] exerts critical regulatory actions in physiology and pathophysiology in many systems. It is present in normal bodily fluids, and is elevated in pathology (1). In vivo, "LPA" exists as distinct molecular species, each having a single fatty acid of varying chain length and degree of unsaturation covalently attached to the glycerol backbone via an acyl, alkyl, or alkenyl link. These species differ in affinities for the individual LPA receptors [(LPARs), LPA1-6] and coupling to G proteins (2). However, LPA 18:1 has been and continues to be the most commonly utilized species in reported studies. The actions of "LPA" remain poorly defined in oral biology and pathophysiology. Our laboratory has addressed this knowledge gap by studying in vitro the actions of the major human salivary LPA species [18:1, 18:0, and 16:0 (3)] in human oral cells (4-7). This includes gingival fibroblasts (GF), which our flow cytometry data from multiple donors found that they express LPA1-5 (6). We have also reported that these species are ten-fold elevated to pharmacologic levels in the saliva and gingival crevicular fluid obtained from patients with moderate-severe periodontitis (8). As the potential of LPA to regulate transcriptional activity had not been examined in the oral system, this study used whole human genome microarray analysis to test the hypothesis that LPA 18:1-treated human GF would show significant changes in gene transcripts relevant to their biology, wound-healing, and inflammatory responses. LPA 18:1 was found to significantly regulate a large, complex set of genes critical to GF biology in these categories and to periodontal disease. The raw data has been deposited at NCBI's GEO database as record GSE57496.

Lysophosphatidic Acid signals through specific lysophosphatidic Acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts.

BACKGROUND: We showed that the pluripotent platelet growth factor and mediator lysophosphatidic acid (LPA) controls key regenerative responses of human gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PDLFs) and positively modulates their responses to platelet-derived growth factor (PDGF). This study determined which LPA receptor (LPAR) subtype(s) LPA signals through to stimulate mitogenic extracellular signal-regulated kinase (ERK) 1/2 signaling and chemotaxis and to elicit intracellular Ca(2+) increases in GFs and PDLFs because many healing responses are calcium-dependent. METHODS: Activation of mitogen-activated protein kinase was determined using Western blotting with an antibody to phosphorylated ERK1/2. Migration responses were measured using a microchemotaxis chamber. GF and PDLF intracellular Ca(2+) mobilization responses to multiple LPA species and LPAR subtype-specific agonists were measured by using a cell-permeable fluorescent Ca(2+) indicator dye. RESULTS: LPA stimulated ERK1/2 phosphorylation via LPA(1)(-3). For GFs, LPA(1) preferentially elicited chemotaxis, and LPA(1-3) for PDLFs, as confirmed using subtype-specific agonists. Elevation of intracellular calcium seems to be mediated through LPA(1) and LPA(3), with little, if any, contribution from LPA(2). CONCLUSIONS: To the best of our knowledge, this study provides the first evidence that LPA signals through specific LPAR subtypes to stimulate human oral fibroblast regenerative responses. These data, in conjunction with our previous findings showing that LPA modulates GF and PDLF responses to PDGF, suggest that LPA is a factor of emerging importance to oral wound healing.

Gender-based differences in satisfaction with academic preparation and practice experiences.

The purpose of this study was to investigate the effect that practice patterns and other variables had on graduates' level of satisfaction with dental school preparation and satisfaction with several career experiences and to determine if any gender-based differences occurred in these findings. Dentists who graduated from Creighton University School of Dentistry between 1985 and 2005 were surveyed regarding demographic factors, practice characteristics, satisfaction with educational preparation, and satisfaction with practice experiences. The response data were analyzed using Spearman's rho, multiple regression analysis, and the Pearson product moment. As a result of this analysis, no statistically significant differences were found between male and female dentists who graduated from Creighton University between 1985 and 2005 with respect to satisfaction with academic preparation and postgraduation practice experiences. The findings indicate that gender is not associated with graduates' level of satisfaction with their academic preparation while in dental school and their practice experiences.

Glandular odontogenic cyst of the mandible: from incidental radiographic discovery to prosthetic reconstruction.

A large multilocular radiolucent lesion involving the anterior mandible was noted incidentally in a 44-year-old woman who sought routine dental treatment. An incisional biopsy revealed that this lesion represented an uncommon developmental odontogenic cyst known as a glandular odontogenic cyst. The lesion was removed surgically, followed by reconstruction with a right anterior iliac crest bone graft. This article reviews the radiographic, clinical, and histopathologic appearance of this rare odontogenic cyst, as well as the surgical management and the patient's subsequent prosthetic rehabilitation.