The etiology of central nervous system tumors (CNSTs) is mainly unknown. Aside from extremely rare genetic conditions, such as neurofibromatosis and tuberous sclerosis, the only unequivocally identified risk factor is exposure to ionizing radiation, and this explains only a very small fraction of cases. Using meta-analysis, gene networking and bioinformatics methods, this dissertation explored the hypothesis that environmental exposures produce genetic and epigenetic alterations that may be involved in the etiology of CNSTs. A meta-analysis of epidemiological studies of pesticides and pediatric brain tumors revealed a significantly increased risk of brain tumors among children whose mothers had farm-related exposures during pregnancy. A dose response was recognized when this risk estimate was compared to those for risk of brain tumors from maternal exposure to non-agricultural pesticides during pregnancy, and risk of brain tumors among children exposed to agricultural activities. Through meta-analysis of several microarray studies which compared normal tissue to astrocytomas, we were able to identify a list of 554 genes which were differentially expressed in the majority of astrocytomas. Many of these genes have in fact been implicated in development of astrocytoma, including EGFR, HIF-1α, c-Myc, WNT5A, and IDH3A. Reverse engineering of these 554 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme (GBM) were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. Lastly, bioinformatics analysis of environmental databases and curated published results on GBM was able to identify numerous potential pathways and gene-environment interactions that may play key roles in astrocytoma development. Findings from this research have strong potential to advance our understanding of the etiology and susceptibility to CNSTs. Validation of our 'key genes' and pathways could potentially lead to useful tools for early detection and novel therapeutic options for these tumors.

For most of the patients with brain tumors and/or epilepsy, surgical resection of brain lesions, when applicable, remains one of the optimal treatment options. The success of the surgery hinges on accurate demarcation of neoplastic and epileptogenic brain tissue. The primary goal of this PhD dissertation is to demonstrate the feasibility of using various optical techniques in conjunction with sophisticated signal processing algorithms to differentiate brain tumor and epileptogenic cortex from normal brain tissue intraoperatively. In this dissertation, a new tissue differentiation algorithm was developed to detect brain tumors in vivo using a probe-based diffuse reflectance spectroscopy system. The system as well as the algorithm were validated experimentally on 20 pediatric patients undergoing brain tumor surgery at Nicklaus Children’s Hospital. Based on the three indicative parameters, which reflect hemodynamic and structural characteristics, the new algorithm was able to differentiate brain tumors from the normal brain with a very high accuracy. The main drawbacks of the probe-based system were its high susceptibility to artifacts induced by hand motion and its interference to the surgical procedure. Therefore, a new optical measurement scheme and its companion spectral interpretation algorithm were devised. The new measurement scheme was evaluated both theoretically with Monte Carlo simulation and experimentally using optical phantoms, which confirms the system is capable of consistently acquiring total diffuse reflectance spectra and accurately converting them to the ratio of reduced scattering coefficient to absorption coefficient (µs’(λ)/µa(λ)). The spectral interpretation algorithm for µs’(λ)/µa(λ) was also validated based on Monte Carlo simulation. In addition, it has been demonstrated that the new measurement scheme and the spectral interpretation algorithm together are capable of detecting significant hemodynamic and scattering variations from the Wistar rats’ somatosensory cortex under forepaw stimulation. Finally, the feasibility of using dynamic intrinsic optical imaging to distinguish epileptogenic and normal cortex was validated in an in vivo study involving 11 pediatric patients with intractable epilepsy. Novel data analysis methods were devised and applied to the data from the study; identification of the epileptogenic cortex was achieved with a high accuracy.

Les gliomes ont des conséquences dévastatrices. La morbidité et la mortalité sont élevées. Les gliomes représentent un groupe hétérogène complexe d'entités pathologiques et aucune cause n'a été identifiée pour la majorité des gliomes. Les données épidémiologiques varient d'une étude à l'autre. Le nombre de chaque sous-type histologique est trop petit, même pour un grand centre de neurochirurgie, pour permettre une bonne recherche sur chaque sous-type de gliome. Les spécificités oncologiques et cliniques (épilepsie, troubles cognitifs, troubles moteurs, etc.) nécessitent une prise en charge et une analyse spécifique. De plus, il est important de recueillir et d'enregistrer tous les nouveaux cas et le suivi sur une grande région ou un pays entier pour permettre des études fondamentales et cliniques de qualité. En effet, les études en population sont la seule façon de connaitre l'impact en pratique des différentes thérapeutiques effectuées. Les sociétés françaises impliquées en neuro-oncologie (Société Française de Neurochirurgie, Société Française de Neuropathologie, Association des Neuro-Oncologues d'Expression Française) ont récemment créé le Recensement national histologique des tumeurs primitives du système nerveux central (RnhTPSNC) ou French Brain Tumor DataBase (FBTDB) en anglais. L'objectif principal du RnhTPSNC est d'enregistrer de manière prospective tous les cas incidents de tumeur primitive du système nerveux central (TPSNC), en France, pour lesquels le diagnostic histologique est confirmé (1-3). Les objectifs à long terme du RnhTPSNC sont de créer un registre histologique et un réseau national pour : (1) réaliser des études épidémiologiques, (2) mettre en place une base de données pour favoriser toute étude clinique ou fondamentale à grande échelle, (3) permettre l'évaluation des pratiques médicales d'une région ou du pays tout entier, (4) harmoniser et optimiser la prise en charge médicale des patients atteints de TPSNC. La présente étudiante en thèse, Sonia Zouaoui, concentrera son travail sur les gliomes. D'abord, elle devra recueillir les données des patients, puis analyser les facteurs pronostiques, la survie et les prises en charges oncologiques. Deuxièmement, elle participera à l'étude de la répartition géographique des principaux types de gliomes et à la recherche de facteurs de causaux. Troisièmement, elle procédera à un inventaire du matériel cryopréservé disponible pour la réalisation d'études translationnelles. / Gliomas have devastating consequences. Morbidity and mortality are high. Gliomas represent a complex heterogeneous group of pathologic entities and no underlying cause has been identified for the majority of them. Epidemiologic data vary from study to study. The number of each histological subtype is too small, even for a big neurosurgical center, to allow a good research on each subtype of glioma. Oncological and clinical specificities (epilepsy, cognitive disorders, motor impairments, etc) require a specific care and analysis. Indeed, we need to collect and record all new cases and follow up in large area, to allow good basic and clinical studies. Furthermore, population study is the only way to know what clinicians do to the patients, and make possible evaluating the medical care. The French societies involved in Neuro-Oncology (Société Française de Neurochirurgie, Société Française de Neuropathologie, Association des Neuro-Oncologues d'Expression Française) have recently created the French Brain Tumor DataBase (FBTDB). The main objective of the FBTDB is to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available (1-3). The long-term goals of the FBTDB are to create a histological national registry and a national network to (1) perform epidemiological studies, (2) implement a new database and use it for setting up both clinical and basic research protocols, (3) allow the evaluation of the medical practices of an area or of the entire country, and (4) harmonize the healthcare of patients affected by PCNST at the higher level. The present PhD student, Sonia Zouaoui, will focus her work on gliomas. First, she will collect data, and will analyze prognostic factors, survival and oncological patterns of care for patients with newly diagnosed glioma in France. Secondly, she will participate in the study of geographical distribution of the main types of glioma and in search of causal factors. Thirdly, she will conduct an inventory of cryopreserved material available for translational research.

abstract: Intraoperative diagnosis in neurosurgery has traditionally relied on frozen and formalin-fixed, paraffin-embedded section analysis of biopsied tissue samples. Although this technique is considered to be the “gold standard” for establishing a histopathologic diagnosis, it entails a number of significant limitations such as invasiveness and the time required for processing and interpreting the tissue. Rapid intraoperative diagnosis has become possible with a handheld confocal laser endomicroscopy (CLE) system. Combined with appropriate fluorescent stains or labels, CLE provides an imaging technique for real-time intraoperative visualization of histopathologic features of the suspected tumor and healthy tissues. This thesis scrutinizes CLE technology for its ability to provide real-time intraoperative in vivo and ex vivo visualization of histopathological features of the normal and tumor brain tissues. First, the optimal settings for CLE imaging are studied in an animal model along with a generational comparison of CLE performance. Second, the ability of CLE to discriminate uninjured normal brain, injured normal brain and tumor tissues is demonstrated. Third, CLE was used to investigate cerebral microvasculature and blood flow in normal and pathological conditions. Fourth, the feasibility of CLE for providing optical biopsies of brain tumors was established during the fluorescence-guided neurosurgical procedures. This study established the optimal workflow and confirmed the high specificity of the CLE optical biopsies. Fifth, the feasibility of CLE was established for endoscopic endonasal approaches and interrogation of pituitary tumor tissue. Finally, improved and prolonged near wide-field fluorescent visualization of brain tumor margins was demonstrated with a scanning fiber endoscopy and 5-aminolevulinic acid. These studies suggested a novel paradigm for neurosurgery-pathology workflow when the noninvasive intraoperative optical biopsies are used to interrogate the tissue and augment intraoperative decision making. Such optical biopsies could shorten the time for obtaining preliminary information on the histological composition of the tissue of interest and may lead to improved diagnostics and tumor resection. This work establishes a basis for future in vivo optical biopsy use in neurosurgery and planning of patient-related outcome studies. Future studies would lead to refinement and development of new confocal scanning technologies making noninvasive optical biopsy faster, convenient and more accurate. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2020

Bakgrund: I Sverige insjuknar ca 2000 personer i hjärntumör varje år. En hjärntumör kan vara antingen elakartad eller godartad, varav den förstnämnda är den vanligaste. Symtomen och prognosen vid en hjärntumör varierar beroende av vilken typ av tumör det handlar om och var i hjärnan tumören sitter. Att drabbas av en hjärntumör kan innebära att personens mening och sammanhang blir påverkat. Sjuksköterskans uppgift är att ge personcentrerad vård för att främja hälsa och lindra lidande. Syfte: Syftet med studien var att belysa upplevelsen av att leva med en hjärntumör.  Metod: En litteraturöversikt genomfördes i enlighet med Fribergs metod. Tio vetenskapliga artiklar hämtades från de tre olika databaser Cinahl Complete, Medline och Psycinfo. Artiklarna var av både kvalitativ och kvantitativ design. Resultat: Litteraturöversikten resulterade i fyra teman som belyser upplevelsen av att leva med en hjärntumör. De fyra temana var: anpassningsstrategier,information, relationer och hopp. Anpassningsstrategier tillämpades i vardagslivet och arbetslivet för att tillvaron skulle fungera. Informationen som gavs av vårdpersonalen upplevdes som bristfällig. Det framkom att närstående var ett viktigt stöd genom hela sjukdomsprocessen, vidare beskrivs tryggheten i att få träffa samma vårdpersonal. Trots sjukdom framkom att deltagarna hade ett inneboende hopp.  Diskussion: Diskussionen är uppdelad i en metoddiskussion och en resultatdiskussion. Litteraturöversiktens styrkor och svagheter diskuterades i metoddiskussionen. I resultatdiskussionen diskuterades resultatet utifrån Katie Erikssons vårdvetenskapliga begrepp hälsa, lidande och vårdande. / Background: About 2000 people get diagnosed with brain tumor each year in Sweden. A brain tumor can be either malignant or nonmalignant where the formeris most common. Symptoms and prognosis varies depending on type of brain tumor and where in the brain it is located. The diagnosis of brain tumor could result in impact a person's meaning and purpose. The responsibility of a nurse is to give person-centered care to promote the health of the patient and relieve suffering. Aim: The aim of the study was to elucidate the experience of living with a brain tumor. Method: A literature review was made accordingly with Friberg’s method. Ten scientific articles were collected from three different databases; Cinahl Complete, Medline and Psycinfo. The articles were of both in qualitative and quantitative design. Results: The literature review as a result showed four themes that would enlighten the experience of living with a brain tumor. Those four themes are: Adjustment strategies, information, relations and hope. Adjustment strategies were used in daily life and work situations, to make the everyday life work. Furthermore, the review showed that the information that were given by the nurses were inadequate. The review described that close relatives were an important support throughout the entire process, further describe the confidence of meeting the same health professionals. Regardless of the tumor the participants describe having an inner hope. Discussion: The discussion is divided into a method discussion and a result discussion. The strengths and weaknesses of the literature review is discussed in the method discussion. The result was discussed from Katie Eriksson’s scientific terms Health, Suffering and Care.

Personer med hjärntumör lever med fysiska, kognitiva och neurologiska symtom beroende på tumörens lokalisation, de lever med osäkra prognoser och oro för framtiden och deras anhöriga. Genom att anta ett holistiskt perspektiv kan sjuksköterskan värna om personens behov och erbjuda stödjande resurser. Litteraturstudiens syfte var att belysa hur vuxna personer med hjärntumör upplever dagligt liv. Studien genomfördes som en allmän litteraturstudie. I studiens resultat framkom att personer upplever begränsningar i vardagen till följd av sina symtom, att de upplever en förändrad psykosocial situation, att de har ett stort behov av information, men även att de har ett inneboende hopp och använder sig av copingstrategier. Sjuksköterskan bör se individen bakom sjukdomen, och uppmärksamma hens behov och önskningar. Informationen bör vara individuellt anpassad efter personens kognitiva förmågor och kommunikation med de anhöriga bör främjas. Sjuksköterskan bör ge emotionellt stöd och på så sätt stödja personen i att acceptera sin livssituation samt finna styrka och hopp. Mer forskning om personer med hjärntumör i arbetsför ålder krävs såsom hur de upplever möjligheten att få information om de långsiktiga konsekvenserna när de återgått till dagligt liv efter behandling. / Persons with brain tumor lives with physical, cognitive and neurological symptoms depending on where the tumor is located, they live with unsure prognosis and anxiety about the future and their relatives. The nurse can protect the needs of the person and offer supporting resources by adopting a holistic approach. The aim of the study was to illustrate how adults with brain tumors experience daily life. The study was conducted as a general literature study. The result of the study illustrates persons experiencing limitations in daily life activities, a changed psychosocial situation, a need for information but also an intrinsic hope and strategies to cope. The nurse should see the individual behind the disease and pay attention to their needs and desires. The information given should be individually customized to the persons cognitive abilities and the communication with their relatives should be promoted. The nurse should give the person emotionally support and by that support the person in accepting their new way of living life and to feel strength and hope. More research about persons with brain tumor in working age is needed, such as how they experience the possibility to recieve information about the long-term consequences when they returned to daily life after treatment.

Brain tumors or brain cancer is a disease than affects people of all ages. The median age of a person living with a brain tumor is 60 years, it is however a disease that affects children and young adults in high grade. Brain cancer is the second most common type of cancer among children and is also the most common cause of cancer related death among this group. To ensure that the damages on the brain is as small as possible, it is important that a tumor can be diagnosed and removed as early as possible. Previous methods of diagnosis is based on biopsy where a part of the tumor is removed and examinated by a pathologist. This is a time consuming process that also is biased by the human factor, there is therefore a need for a method that can be used \textit{in situ} with an unbiased result. One method that have shown great promise is photensitation with 5-Aminolevoluic acid (5-ALA). However, this method have shown to only work properly on tumors of high malignancy in adults. As a comlpiment to photosentisation, Raman spectroscopy have shown good promise in previous studies.  This study was conducted to investigate the use of Raman spectroscopy as a tool for \textit{in situ} brain tumor diagnostics. The use of Raman spectroscopy was tested by comparing two previously performed studies, where they looked at a number of Raman bands from biological markers that are known to change in cancerous tissue as well as the intensity ratio between some Raman bands.  A measurement system for Raman spectroscopy was designed and built at Luleå University of Technology where the system were evaluated on tissue samples from conventional meat i.e. pork and beef to ensure that is was possible to achieve spectroscopic information of protein and lipid content in tissue. The measurement system was then transported to Linköpings University where the measurements on six brain tissue samples where performed. The samples came from five different tumors of which one tumor was thought to come from a high malignant tumor based on preliminary histopathological analysis and four from low malignant or benign tumors. Two samples where obtained from the high malignant tumor that was photosentisized with 5-Aminolevoluic acid and one of the samples where illuminated with blue light prior to the Raman spectroscopic measurements.  The spectroscopic data was pre-processed before analysis using conventional methods. The analysed spectra from the brain tissue samples showed presence of the Raman bands associated with brain tissue. It was also possible to see Raman bands associated with 5-ALA in the samples that had been photosentisized, however when the tissue had been illuminated with blue light it was also possible to see distinct Raman bands associated with brain tissue. One tissue sample also showed presence of reduced Neuroglobin (NGB). The composition of NGB is also known to change in tumorous tissue and could therefore be used in future work as a biological marker for brain tumors. When comparing the results obtained in this study with the two previously performed, one of the studies showed that two samples were from a tumor of high malignancy and the other from low malignant or benign tumors. This result was in accordance with the preliminary histopathological assessment of the brain tissue samples. When comparing the results to the other study, the results where contradictory and indicated that all tissue samples where from low malignant or benign tumors.  The conclusion of this work is that Raman spectroscopy is possible to use as a tool for brain tumor diagnostics. It would be desirable to use this method in combination with 5-ALA staining since the Raman bands from brain tissue could be resolved when the tissue had been illuminated with blue light. / Hjärntumörer kan drabba människor i alla åldrar, medelåldern för människor som lever med en hjärntumör är 60 år, men det är ett tillstånd som även drabbar barn och unga i stor utsträckning. Hjärntumörer är den näst vanligaste cancerformen hos barn och är även den främsta orsaken till cancerrelaterad död i den åldergruppen. För att minimera skadorna på hjärnan är det viktigt att en tumör kan lokaliseras och tas bort så tidigt som möjligt. De metoder som används idag bygger framför allt på biopsi, där en del av tumören tas bort och undersöks av en histopatalog. Det är en process som tar lång tid och även påverkas av den mänskliga faktorn, det finns därmed ett behov av en metod som kan avändas \textit{in situ} som ger ett resultat som inte påverkas av den mänskliga faktorn. En metod som har visat lovande resultat är fotosensibilisering med 5-Aminolevulinsyra (5-ALA). Desvärre har den metoden bara visat sig fungera bra för högmaligna tumörer hos vuxna. Som ett komplement till fotosensibilisering har Ramanspektroskopi visat lovande resultat i tidigare genomförda studier.  Det här arbetet genomfördes för att undersöka användningen av Ramanspektroskopi som ett verktyg för diagnostisering av hjärntumörer. Som grund användes två tidigare genomförda studier där de undersökte Ramanband från biologiska markörer i hjärnvävnad som ändras i cancerogen vävnad. De undersökte även hur den biokemiska sammansättningen av hjärnvävnaden ändrades genom att jämföra intensiteten av olika Ramanband.  Ett mätsystem för Ramanspektroskopi designades och byggdes upp på Luleå Tekniska Universitet där det även testades på vävnad från kött (fläsk och biff). Därefter transporterades mätsystemet till Linköpings Universitet för att genomföra mätningar på sex olika vävnadsprov från fem hjärntumörer av olika malignitet. Baserat på en preliminär histopatalogisk bedömning var en av tumörerna högmalignt och de fyra andra tumörerna var antingen lågmalignta eller benigna. Två av proverna som undersöktes kom från den högmalignta tumören som även var fotosensibilierad med 5-Aminolevulinsyra, varav ett av proverna var belyst med blått ljus innan de Ramanspektroskopiska mätningarna genomfördes.  Innan resultatet från Ramanspektroskopiska mätningarna analyserades behandlades datan med konventionella metoder i MatLab. I de resulterade spektrumen gick det att se tydliga Ramanband associerade med hjärnvävnad. Det gick även att se Ramanband associerade med 5-ALA i de två prover som var fotosensibiliserade och i det provet som var belyst med blått ljus innan de spektroskopiska mätningarna gjordes gick det även att se tydliga Ramanband associerade med hjärnvävnad. När resultatet analyserades gick det även att se spektra associerat med reducerat Neuroglobin (NGB) i ett av proverna. Sammansättningen av NGB är också någonting som ändras i cancerogen vävnad och skulle därför också kunna användas som en bilogisk markör för hjärntumörer i framtida studier.  När resultaten från den här studien jämfördes med de tidigare studierna indikerade den ena studien att två av vävnadsproverna kom från en högmalignt tumör och att de resterande fyra från lågmaligna eller benigna tumörer, vilket stämmer överens med den preliminära diagnosticeringen av tumörerna. När resultatet istället jämfördes med den andra studien stämde inte resultatet lika bra med den preliminära diagnosticeringen av tumörerna. Metoden presenterad av Zhou m.fl. indikerade att alla tumörer kom från lågmaligna eller benigna tumörer.  Slutsaten av det här arbetet är att Ramanspektroskopi skulle kunna användas som en metod för diagnosticering av hjärntumörer. Metoden skulle även fungera bra som ett komplement till fotosensibilisering med 5-ALA eftersom att det var möjligt att se Ramanband associerade med hjärnvävnad när vävnaden hade belysts med blått ljus.

Bakgrund: Primär malign hjärntumör medför en tung symtombörda som yttrar sig i en stor variation av fysiska, kognitiva och neurologiska symtom som berör patientens funktionsförmåga och psykiska välmående. Utöver den emotionella och existentiella påfrestningen av att leva med en cancersjukdom ingår hos hjärntumörsjuka patienter även en sviktande kognitiv komponent. Syfte: Syftet med denna litteraturöversikt var att belysa psykologiska påfrestningar för vuxna patienter med primär malign hjärntumör. Metod: Studien utfördes som en allmän litteraturöversikt där tiovetenskapliga kvalitetsgranskades och analyserades för att sedan delas in i tre stycken övergripande teman. Resultat: Det första temat, Osäkerheten i prognosen, belyser den ovisshet som uppstod till följd en oförutsägbar framtid och behovet av mer information gällandes behandlingsmöjligheter och vilka symtom som kan väntas drabba dem. Temat Psykosociala konsekvenser beskriver hur patienter kände att de förlora sig själva i sjukdomen på grund av minnespåverkan, personlighetsförändringaroch en oförmåga att upprätthålla den livsstil som de tidigare haft. Gemensamt bland de sjuka var en rädsla för att vara en börda för dem i patientens närhet och en oro om att förlora sin självständighet. Den existentiella konfrontationen talar om de oundvikliga tankarna om döden och om hoppets betydelse. / Background: Primary malignant brain tumor carries a heavy symptom burden that presents itself in a big variation of physical, cognitive and neurological symptoms that affects the patients functioning and psychological wellbeing. Along with the emotional and existential stress of living with cancer, patients diagnosed with brain cancer also suffer from cognitive dysfunction. Purpose: The aim of this study was to illustrate the psychological strain of adult patients living with primary malignant brain tumor. Method: The study was executed as a general literature review based on ten scientific articles. The articles were quality-tested and analyzed to later be sorted into three main themes. Results: The first theme, The uncertainty in the prognosis, illuminate the uncertainty that occurred due to an unpredictable future and the need of information concerning treatment options and what symptoms to expect. The theme The psychosocial consequences, describes how the patients felt as though they had lost themselves to the disease due to memory loss, personality disorders and the inability to maintain the lifestyle they previously had. The patients shared a fear of being a burden to the people around them and a concern of losing their independency. The existential confrontation speaks about the inevitable thoughts of death and the importance of hope.

Background: Near-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor. Methods: Self-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation. Results: The loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 and 26nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner. Conclusion: The IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.

No description available.