Cadmore media player playing video Qualitative head-to-head comparison of headlamp and microscope for visualizing 5-ALA fluorescence during resection of glioblastoma
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Qualitative head-to-head comparison of headlamp and microscope for visualizing 5-ALA fluorescence during resection of glioblastoma
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Qualitative head-to-head comparison of headlamp and microscope for visualizing 5-ALA fluorescence during resection of glioblastoma
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https://cadmoremediastorage.blob.core.windows.net/b8ac7c01-79ec-4799-909a-dba68c7f39bf/videoscrubberimages/Scrubber_306.jpg
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T00H10M08S
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https://stream.cadmore.media/player/b8ac7c01-79ec-4799-909a-dba68c7f39bf
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https://cadmoreoriginalmedia.blob.core.windows.net/b8ac7c01-79ec-4799-909a-dba68c7f39bf/21-181.mp4?sv=2019-02-02&sr=c&sig=tPeprEKVwqu6BVodwosb3ZRep0XG%2Bntz0DAmw1EzXyE%3D&st=2025-05-13T19%3A42%3A35Z&se=2025-05-13T21%3A47%3A35Z&sp=r
Upload Date:
2021-11-22T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
SPEAKER 1: Fluorescence-guided surgery for high-grade glioma has become a new standard of care in the United States following FDA approval of 5-aminolevulinic acid, trade name Gleolan. Patient ingestion of precursor molecule 5-ALA several hours before resection allows it to pass through an open blood-brain barrier, preferentially into tumor cells where it becomes metabolized into the fluorescent drug protoporphyrin IX.
SPEAKER 1: Studies have demonstrated not only safety but increases in progression-free survival in comparison to microsurgery without fluorescence. Though neurosurgical microscopes have incorporated filters into their systems to permit this fluorescence-guided approach, improved visualization techniques remain a paramount interest for glioma surgeons. One solution has been to develop a wearable fluorescence-guided headlamp for excitation of the fluorophore in association with absorption filters built into surgical loupes to remove extraneous or distracting wavelengths.
SPEAKER 1: In this video, we present a man with glioblastoma who underwent fluorescence-guided surgery in which similar images of the operative field were acquired, alternating between the microscope and a new commercially-available headlight, facilitating the comparison of visualization quality between the two devices. We also review some of the principles of fluorescence guidance surgery that may explain the differences we observed between the microscope and the headlamp.
SPEAKER 1: To review, both illumination devices create a uniform beam of light with wavelength of approximately 405 nm. 405-nm light corresponds to the peak absorption spectrum of protoporphyrin IX, allowing for its excitation and emission of lower-energy photons at approximately 630 nm. 405-nm light that does not strike protoporphyrin IX reflects from the tissue. This results in two spectral beams of light, reflected blue from nontumor and newly formed fluorescent red from tumor returning through the optical filter of the microscope or loupes that attenuate intensity of the violet-blue light but permit the passage of the red light.
SPEAKER 1: Since both 405- and 630-nm light are within the dynamic range sensitivity of a human eye, we can perceive the image as shades of blue and red, thereby enabling a visual distinction between neoplastic and nonneoplastic tissue. While the positive predictive value of 5-ALA fluorescence has approached 100% in most high-grade gliomas series, its negative predictive value in surgeries using microscope filter has ranged from 22% to 69% in a recent review, a finding partly explained by the extensively infiltrating nature of high-grade gliomas and partly from the lack of blood-brain barrier breakdown in peripheral regions with lower-density tumor infiltration.
SPEAKER 1: In this case, an 85-year-old left-handed Russian-speaking man presented with worsening word-finding difficulty. Examination revealed dysnomia and dyscalculia. MRI of the brain revealed a heterogeneously-enhancing mass in the left temporal lobe with an adjacent satellite nodule, likely a glioblastoma. Neuropsychological testing confirmed candidacy for awake language mapping.
SPEAKER 1: The patient was administered 5-ALA oral solution, 20 mg/kg, 3 hours prior to surgery. He was taken to the operating theater. Under local anesthesia with conscious sedation, a head clamp was applied and secured to the bed where navigation was registered. A wide craniotomy was performed over the tumor. The patient was awakened and language mapping was performed in both English and Russian to outline a safe corticectomy.
SPEAKER 1: No essential language areas were found overlying the expected incision. Fluorescence-guided resection was performed, alternating between the microscope and headlamp. Headlamp images were created using a high-definition LED headlight, TriBeam HD Headlight firmware version 1.0, Powerpack firmware version 2.0, Designs for Vision, emitting 405- and 450-nm wavelength light combined with loupes containing filters that block light beneath 430 nm.
SPEAKER 1: The loupes contained two filters in each telescope and one in the carrier lens that provides emission filtering in both the magnification and eyeglass lens optics. The headlamp system features a wireless Bluetooth foot pedal pairing function to alternate between natural light and filtered light. Headlamp images were recorded using an iPhone 12 Pro camera paired with a smartphone filter adapter. Microscope images were acquired using the built-in system.
SPEAKER 1: Theater lights were turned down during fluorescence visualization. Microscope images were recorded directly through the microscope. The conventional microscope, a Zeiss KINEVO, was activated into BLUE 400 fluorescence mode for protoporphyrin IX visualization. As demonstrated in the video, protoporphyrin IX fluorescence provided by the headlamp is dramatically brighter than provided by the microscope.
SPEAKER 1: Indeed, the headlamp visualization provided a sharper contrast between tumor and normal brain in both the resection cavity and ex vivo in the specimen table. The headlamp performed especially well when the cavity contained blood, since hemoglobin absorbs much of the light in the fluorescent emission spectrum, thereby obfuscating fluorescence detection. Three groups of factors affect the intensity of protoporphyrin IX fluorescence.
SPEAKER 1: First, those related to the excitation light, such as 1) light power, 2) distance to the tissue, 3) excitation light spectrum, and 4) light beam shape. Second, those related to the fluorophor in the tissue, including 1) timing of surgery within the optimal window of maximal protoporphyrin IX accumulation, 2) blood products obscuring the excitation light, and 3) degradation of fluorescence over time due to photobleaching.
SPEAKER 1: The third category are factors related to the detection device, such as 1) distance from the tissue to the detector, 2) sensitivity of the detector, 3) exposure time, and 4) spectrum width that is being detected, as well as 5) any splitting of the emitted light into different pathways by the hardware. This headlamp employs a powerful excitation source that allows for robust protoporphyrin IX excitation at the optimal spectral range.
SPEAKER 1: Light power density depends on the working distance between source and target as presented in this graph. Assuming the shape of the headlamp, illumination light beam is similar to the Zeiss microscope, the curve presented on the graph can be approximated to the headlamp. The graph, based on previously reported data for the Zeiss microscope, equates a headlamp position 43 cm or 17 inches from target with about the same light density as a microscope in BLUE 400 mode, positioned at 25 cm or 10 inches from the target.
SPEAKER 1: By attaching to the surgeon's forehead, the source of the excitation moves with the gaze of the surgeon more quickly than the microscope, which must be moved separately. Moreover, rather than employing a hand switch as used by the microscope, the headlamp utilizes a wireless pedal that allows for rapid alternation between white light and two different settings of the blue light to optimize visualization of the surrounding brain so the surgeon can work under blue light.
SPEAKER 1: Using pure 405-nm excitation, the operator would mostly see red protoporphyrin IX fluorescence on a background that is close to normal colors. The second mode, blending 405- and 450-nm excitation lights together, includes red fluorescent light, but also surrounding tissue without protoporphyrin IX that appears bluish because of reflected 450-nm light, thereby enhancing contrast between tissue types.
SPEAKER 1: Here we show a diagram of the power of the excitation blue light measured at various distances from the microscope. Greater excitation power creates brighter fluorescence. Therefore, a headlight used at 17 inches from the tissue, labeled as a star, has greater blue light power than a surgical microscope positioned at the same distance, and comparable excitation power to when the microscope is used at the usual distance from the tissue.
SPEAKER 1: Additionally, TriBeam HD Headlight uses a longpass filter that allows 91% of light transmission efficiency, which is devoid of the complex microscope optical system, including its beam splitter, which inevitably reduces efficiency of eventual light transmission to the surgeon's eye or the microscope camera. Surgical loupes attached to the headlamp are manufactured with either a x2.5 or x3.5 magnification, versus the Zeiss microscope which may achieve up to x10 to x12 magnification at 30 cm.
SPEAKER 1: One limitation to this comparative study is that digital recordings from different systems that may misrepresent what the surgeon's eye is receiving through the microscope oculars. Light entering the microscope splits on its way to the camera, decreasing brightness relative to the surgeon's actual view. We present a better approximation of the surgeon's ocular view by increasing the still-image brightness by 60%.
SPEAKER 1: Unfortunately, a tumor-brain ratio, TBR, comparison cannot be performed in this study, because the data are not within the dynamic range due to the microscope images being underexposed for red light. REVEAL images of this study show a TBR of 4. Further study of headlamp-assisted fluorescence-guided surgery will determine whether this technology can improve on the negative predictive value of 5-ALA and ensure that there are not excessive false positives.
SPEAKER 1: Such a study will require analysis of histological specimen. This patient recovered in a light-regulated environment for 48 hours according to institutional protocol. Postoperative MRI confirmed gross-total resection including the satellite nodule. The patient was monitored after an episode of confusion on postoperative day 2, but this resolved and EEG showed no seizures.
SPEAKER 1: He was discharged to home 5 days after surgery and seen in follow-up with no complications and referred to neuro-oncology to begin his adjuvant care.
Segment:0 .
[MUSIC PLAYING]
SPEAKER 1: Fluorescence-guided surgery for high-grade glioma has become a new standard of care in the United States following FDA approval of 5-aminolevulinic acid, trade name Gleolan. Patient ingestion of precursor molecule 5-ALA several hours before resection allows it to pass through an open blood-brain barrier, preferentially into tumor cells where it becomes metabolized into the fluorescent drug protoporphyrin IX.
SPEAKER 1: Studies have demonstrated not only safety but increases in progression-free survival in comparison to microsurgery without fluorescence. Though neurosurgical microscopes have incorporated filters into their systems to permit this fluorescence-guided approach, improved visualization techniques remain a paramount interest for glioma surgeons. One solution has been to develop a wearable fluorescence-guided headlamp for excitation of the fluorophore in association with absorption filters built into surgical loupes to remove extraneous or distracting wavelengths.
SPEAKER 1: In this video, we present a man with glioblastoma who underwent fluorescence-guided surgery in which similar images of the operative field were acquired, alternating between the microscope and a new commercially-available headlight, facilitating the comparison of visualization quality between the two devices. We also review some of the principles of fluorescence guidance surgery that may explain the differences we observed between the microscope and the headlamp.
SPEAKER 1: To review, both illumination devices create a uniform beam of light with wavelength of approximately 405 nm. 405-nm light corresponds to the peak absorption spectrum of protoporphyrin IX, allowing for its excitation and emission of lower-energy photons at approximately 630 nm. 405-nm light that does not strike protoporphyrin IX reflects from the tissue. This results in two spectral beams of light, reflected blue from nontumor and newly formed fluorescent red from tumor returning through the optical filter of the microscope or loupes that attenuate intensity of the violet-blue light but permit the passage of the red light.
SPEAKER 1: Since both 405- and 630-nm light are within the dynamic range sensitivity of a human eye, we can perceive the image as shades of blue and red, thereby enabling a visual distinction between neoplastic and nonneoplastic tissue. While the positive predictive value of 5-ALA fluorescence has approached 100% in most high-grade gliomas series, its negative predictive value in surgeries using microscope filter has ranged from 22% to 69% in a recent review, a finding partly explained by the extensively infiltrating nature of high-grade gliomas and partly from the lack of blood-brain barrier breakdown in peripheral regions with lower-density tumor infiltration.
SPEAKER 1: In this case, an 85-year-old left-handed Russian-speaking man presented with worsening word-finding difficulty. Examination revealed dysnomia and dyscalculia. MRI of the brain revealed a heterogeneously-enhancing mass in the left temporal lobe with an adjacent satellite nodule, likely a glioblastoma. Neuropsychological testing confirmed candidacy for awake language mapping.
SPEAKER 1: The patient was administered 5-ALA oral solution, 20 mg/kg, 3 hours prior to surgery. He was taken to the operating theater. Under local anesthesia with conscious sedation, a head clamp was applied and secured to the bed where navigation was registered. A wide craniotomy was performed over the tumor. The patient was awakened and language mapping was performed in both English and Russian to outline a safe corticectomy.
SPEAKER 1: No essential language areas were found overlying the expected incision. Fluorescence-guided resection was performed, alternating between the microscope and headlamp. Headlamp images were created using a high-definition LED headlight, TriBeam HD Headlight firmware version 1.0, Powerpack firmware version 2.0, Designs for Vision, emitting 405- and 450-nm wavelength light combined with loupes containing filters that block light beneath 430 nm.
SPEAKER 1: The loupes contained two filters in each telescope and one in the carrier lens that provides emission filtering in both the magnification and eyeglass lens optics. The headlamp system features a wireless Bluetooth foot pedal pairing function to alternate between natural light and filtered light. Headlamp images were recorded using an iPhone 12 Pro camera paired with a smartphone filter adapter. Microscope images were acquired using the built-in system.
SPEAKER 1: Theater lights were turned down during fluorescence visualization. Microscope images were recorded directly through the microscope. The conventional microscope, a Zeiss KINEVO, was activated into BLUE 400 fluorescence mode for protoporphyrin IX visualization. As demonstrated in the video, protoporphyrin IX fluorescence provided by the headlamp is dramatically brighter than provided by the microscope.
SPEAKER 1: Indeed, the headlamp visualization provided a sharper contrast between tumor and normal brain in both the resection cavity and ex vivo in the specimen table. The headlamp performed especially well when the cavity contained blood, since hemoglobin absorbs much of the light in the fluorescent emission spectrum, thereby obfuscating fluorescence detection. Three groups of factors affect the intensity of protoporphyrin IX fluorescence.
SPEAKER 1: First, those related to the excitation light, such as 1) light power, 2) distance to the tissue, 3) excitation light spectrum, and 4) light beam shape. Second, those related to the fluorophor in the tissue, including 1) timing of surgery within the optimal window of maximal protoporphyrin IX accumulation, 2) blood products obscuring the excitation light, and 3) degradation of fluorescence over time due to photobleaching.
SPEAKER 1: The third category are factors related to the detection device, such as 1) distance from the tissue to the detector, 2) sensitivity of the detector, 3) exposure time, and 4) spectrum width that is being detected, as well as 5) any splitting of the emitted light into different pathways by the hardware. This headlamp employs a powerful excitation source that allows for robust protoporphyrin IX excitation at the optimal spectral range.
SPEAKER 1: Light power density depends on the working distance between source and target as presented in this graph. Assuming the shape of the headlamp, illumination light beam is similar to the Zeiss microscope, the curve presented on the graph can be approximated to the headlamp. The graph, based on previously reported data for the Zeiss microscope, equates a headlamp position 43 cm or 17 inches from target with about the same light density as a microscope in BLUE 400 mode, positioned at 25 cm or 10 inches from the target.
SPEAKER 1: By attaching to the surgeon's forehead, the source of the excitation moves with the gaze of the surgeon more quickly than the microscope, which must be moved separately. Moreover, rather than employing a hand switch as used by the microscope, the headlamp utilizes a wireless pedal that allows for rapid alternation between white light and two different settings of the blue light to optimize visualization of the surrounding brain so the surgeon can work under blue light.
SPEAKER 1: Using pure 405-nm excitation, the operator would mostly see red protoporphyrin IX fluorescence on a background that is close to normal colors. The second mode, blending 405- and 450-nm excitation lights together, includes red fluorescent light, but also surrounding tissue without protoporphyrin IX that appears bluish because of reflected 450-nm light, thereby enhancing contrast between tissue types.
SPEAKER 1: Here we show a diagram of the power of the excitation blue light measured at various distances from the microscope. Greater excitation power creates brighter fluorescence. Therefore, a headlight used at 17 inches from the tissue, labeled as a star, has greater blue light power than a surgical microscope positioned at the same distance, and comparable excitation power to when the microscope is used at the usual distance from the tissue.
SPEAKER 1: Additionally, TriBeam HD Headlight uses a longpass filter that allows 91% of light transmission efficiency, which is devoid of the complex microscope optical system, including its beam splitter, which inevitably reduces efficiency of eventual light transmission to the surgeon's eye or the microscope camera. Surgical loupes attached to the headlamp are manufactured with either a x2.5 or x3.5 magnification, versus the Zeiss microscope which may achieve up to x10 to x12 magnification at 30 cm.
SPEAKER 1: One limitation to this comparative study is that digital recordings from different systems that may misrepresent what the surgeon's eye is receiving through the microscope oculars. Light entering the microscope splits on its way to the camera, decreasing brightness relative to the surgeon's actual view. We present a better approximation of the surgeon's ocular view by increasing the still-image brightness by 60%.
SPEAKER 1: Unfortunately, a tumor-brain ratio, TBR, comparison cannot be performed in this study, because the data are not within the dynamic range due to the microscope images being underexposed for red light. REVEAL images of this study show a TBR of 4. Further study of headlamp-assisted fluorescence-guided surgery will determine whether this technology can improve on the negative predictive value of 5-ALA and ensure that there are not excessive false positives.
SPEAKER 1: Such a study will require analysis of histological specimen. This patient recovered in a light-regulated environment for 48 hours according to institutional protocol. Postoperative MRI confirmed gross-total resection including the satellite nodule. The patient was monitored after an episode of confusion on postoperative day 2, but this resolved and EEG showed no seizures.
SPEAKER 1: He was discharged to home 5 days after surgery and seen in follow-up with no complications and referred to neuro-oncology to begin his adjuvant care.
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