Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Haj‐Hosseini, Neda; Richter, Johan; Hallbeck, Martin; Wårdell, Karin

doi:10.1016/j.pdpdt.2015.03.004

Cited by 31 publications

(31 citation statements)

References 19 publications

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“…However, such a study requires co-registration of the preoperative and postoperative images to estimate the trajectory which is subject to change in position due to brain shift. In the few studies investigating the effect of ALA dose on the diagnostic performance, no evidence is reported on the improvement or degradation of sensitivity and specificity of fluorescence in the tumor using a lower or higher dose of ALA [24,36]. In this study 20 mg/kg ALA was chosen as that is the current conventional dose of Gliolan [37].…”

Section: Ppix Fluorescencementioning

confidence: 99%

“…In an earlier study the detection of 5-ALA induced PpIX fluorescence was implemented with double excitation wavelengths (337 and 405 nm) for a more precise quantification in several stereotactic procedures and compared to histology and magnetic resonance (MR) spectroscopy [22,23]. A recent fluorescence system adapted to the operating room (OR) environment with single excitation wavelength (405 nm) was later on developed and used in over 50 high grade glioma resections as a stand-alone system [24] or in combination with a surgical fluorescence microscope [25]. The tumor tissue could be detected with over 90% sensitivity compared to histopathology [24,25].…”

Section: Introductionmentioning

confidence: 99%

“…A recent fluorescence system adapted to the operating room (OR) environment with single excitation wavelength (405 nm) was later on developed and used in over 50 high grade glioma resections as a stand-alone system [24] or in combination with a surgical fluorescence microscope [25]. The tumor tissue could be detected with over 90% sensitivity compared to histopathology [24,25]. Moreover, the intensity of PpIX fluorescence could be related to the low and high malignancy grades, infiltrated and non-infiltrated gliosis in the tumor marginal zone.…”

Section: Introductionmentioning

confidence: 99%

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5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy

Haj‐Hosseini¹,

Richter²,

Milos³

et al. 2018

Biomed. Opt. Express

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A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and realtime detection of tumor tissue and microvascular blood flow for tracking the vessels.

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Section: Ppix Fluorescencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy

Haj‐Hosseini¹,

Richter²,

Milos³

et al. 2018

Biomed. Opt. Express

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“…As expected, no PpIX fluorescence was detected in the skin of the patients when using ALA dose of 5 mg∕kg, which further reduces the risk of cutaneous phototoxicity. 17 …”

Section: Protoporphyrin IX Fluorescencementioning

confidence: 99%

Fluorescence-guided resection of brain tumor: review of the significance of intraoperative quantification of protoporphyrin IX fluorescence

et al. 2017

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Abstract. Surgical removal of tumor mass is a common approach in the management of brain tumors. However, the precise delineation of normal tissue from tumor tissue for a complete resection of tumor mass in brain tumor surgery remains a difficult task for neurosurgeons. Aminolevulinic acid (ALA)-mediated exgogenous fluorescence of protoporphyrin IX (PpIX) is a sensitive approach for tumor imaging. Recent studies suggest that the use of ALA/PpIX-mediated fluorescence-guided resection (FGR) or fluorescence-guided surgery can enable more accurate and complete resection of brain tumors, especially when used in quantitative fashion. This review will highlight the current progress in PpIX-mediated FGR and discuss technical challenges in intraoperative quantification of intracellular PpIX fluorescence during FGR of brain tumor.

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“…In another on-going project (EudraCT 2013-005565-40) at the Depts. of Neurosurgery and Biomedical Engineering, in which children with malignant gliomas are operated by means of FGS, observations imply a different metabolism of 5-ALA compared to adults; postoperative skin measurements (Haj-Hosseini et al, 2015) have shown slight fluorescence in adults, but not in the children examined so far. Obviously, we need to understand more about the effects of 5-ALA in the human brain and in malignant brain tumors.…”

Section: Discussionmentioning

confidence: 93%

Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe

Richter¹

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Malignant gliomas grow infiltrative in the brain and can therefore not be completely removed by neurosurgical means. However, for an optimized oncological treatment it has proven useful to resect as much as possible of the tumor tissue. The identification of the tumor in the marginal zone is difficult but crucial. Studies have shown that visualization of the specific enhancement of 5-aminolevulinic acid (5-ALA) in the tumor can help to maximize the resection. The Department of Biomedical Engineering, Linköping University, has developed an optical hand-held probe (HHP) to identify tumor tissue with a high sensitivity by means of fluorescence spectroscopy. The technical design and the optical properties of the probe were gradually developed in a standard neurosurgical setting during resection of malignant gliomas. The device could easily be implemented in the operating room, meeting all requirements in terms of sterile handling and without interference of any kind with other equipment. The integration of the device in a navigation system and its use in combination with a blue light surgical microscope were simple. Measurements in 27 operations during resection of malignant gliomas were compared to results from biopsies from the same tumor locations. The equipment was tested as a stand-alone device (n = 180), integrated in a navigation system or in combination with the blue light microscope (n = 190). A ratio calculated from the measurements enabled objective and comparable values for different tissue types, in correspondence with the findings from the histopathological examinations and in accordance with the navigation system as well as with the surgical microscope. The marginal zone was explored and tumor fluorescence could be identified beyond the fluorescence as seen through the microscope. A higher sensitivity of the HHP was confirmed; the specificity was lower. The combined use of the HHP with a navigation system and with a surgical microscope was beneficial. X XI SammanfattningMaligna hjärntumörer växer infiltrerande i hjärnan och kan därför inte helt avlägsnas genom kirurgiska operationer. För en optimerad behandling har det emellertid visat sig vara av värde att avlägsna så mycket som möjligt av tumörvävnaden. Identifiering av tumören i gränszonen är mycket svårt, men avgörande. Studier har visat att visualisering av den specifika laddningen av 5-aminolevulinsyra (5-ALA) i tumören kan bidra till att maximera resektionen. Institutionen för Medicinsk Teknik (IMT) på Linköpings universitet, har utvecklat en liten handhållen optisk prob (HHP) för att identifiera tumörvävnad med hög känslighet med hjälp av fluorescens-spektroskopi. Den tekniska konstruktionen och de optiska egenskaperna hos proben utvecklades stegvis genom testning i flera neurokirurgiska operationer för resektion av maligna gliom. Utrustningen uppfyllde alla krav när det gällde steril hantering i operationssalen och kunde användas utan störningar av något slag med annan operationsutrustning. Integreringen i ett navigerings-system och a...

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Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Cited by 31 publications

References 19 publications

5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy

5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy

Fluorescence-guided resection of brain tumor: review of the significance of intraoperative quantification of protoporphyrin IX fluorescence

Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe

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