WO2023037382A1

WO2023037382A1 - An apparatus for detection of malignant tumours

Info

Publication number: WO2023037382A1
Application number: PCT/IN2022/050794
Authority: WO
Inventors: Sarang Gotecha; Ashish Chugh
Original assignee: Neurocula Pvt. Ltd.; Dr.D.Y.Patil Vidyapeeth Pune - Deemed To Be University
Priority date: 2021-09-07
Filing date: 2022-09-06
Publication date: 2023-03-16

Abstract

A handy, low cost, user-friendly, portable apparatus for detection of cancer cells is described herein. Further, the apparatus is adapted as a fluorescein guided device. The apparatus primarily comprises of a head assembly having multiple degrees of freedom; a base; and a flexible connecting body. The present invention further discloses a method of detection of malignant tumor with the help of the said apparatus.

Description

“AN APPARATUS FOR DETECTION OF MALIGNANT TUMOURS”

FIELD OF INVENTION:

[001] The present invention generally relates to effective detection of cancer cells . More particularly, the present invention relates to a low cost, user friendly apparatus to identify malignant tumors.

BACKGROUND OF INVENTION:

[002] Tumor is the abnormal growth of the cells that is caused by uncontrolled division of cells, and the cells do not die when they should. Tumors are broadly classified into two categories, namely benign and malignant. The benign tumors are the cells that grow slow, generally remain local, have distinct borders and do not invade other parts of the body. Except in few conditions, the benign tumor does not grow back and therefore is considered as non-cancerous. Malignant tumors are cancerous cells that grow uncontrollably and spread to the distant parts of the body. The malignant tumor usually grows back even after removal and hence considered as worrisome tumor.

[003] Malignant brain tumors such as high grade gliomas (HGG) or cerebral metastasis are devastating diseases. High grade Gliomas, are the most common primary malignant brain tumors in adults and are associated with a poor prognosis despite maximal treatment with combination therapy involving surgery, chemotherapy and radiotherapy. Common detection methods involve MRI, CT scan.

[004] Recent studies have identified a strong correlation between removal extent of glioblastoma and overall survival, wherein the maximal survival occurs when resection volume is greater than 98%, and the surgery is followed by adjuvant radiotherapy and chemotherapy. Hence, early and accurate detection of glioblastoma is essential step in such a treatment. The accurate intraoperative detection of the tumor cells/tissues under the microscope is challenging due to the similarity between the normal cells/tissues and tumor cells/tissues.

[005] The precise intraoperative removal of the tissues largely depends upon the surgeon’s expertise, as finding out the location of the tissues under the white light is a matter of judgment of the surgeon. Emergence of fluorescence guided surgeries (FGS) have made the task relatively easy for the surgeons, as FGS allows the surgeon to differentiate between the abnormal cells or tumor cells against the normal cells, which acts as a biomarker, causing the tumor cells/tissues glow when impinged with a light of an appropriate frequency. The glowing cells guide the surgeons to differentiate the tumor cells/tissues from the normal ones. This not only helps the surgeon in knowing the precise location, margin as well as other critical data of the tumor cells, but also prevents unnecessary damage to the normal or healthy tissues.

[006] Recently, Fluorescein sodium, an organic dye, is used to detect malignant tumor. Fluorescein sodium has gained a relative popularity owing to certain drawbacks in other fluorescence substance, such as cost and reportedly no adverse reaction to any human organ. Further, it is visible to the naked eye at relatively high dosage. Fluorescein sodium illuminates when the incident light, having the wavelength between 465 nm and 490 nm, falls on it. Further, Fluorescein sodium has a peak emission between 520 nm and 530 nm. As a result, Fluorescein sodium emits yellowish - green light when illuminated with incident light. Therefore, an optical instrument is required to capture said yellowish - green light.

[007] Such an instrument is available in the form of high end microscopes, involving very high cost. The issue of the cost is not just a matter of numbers. The issue of accessibility is directly related to the cost. Not all hospitals can afford such a high end device in a developing country. Since the microscope is accompanied with a bulky illuminating system, the entire apparatus is not portable per se. The said practical constraints limit quick and efficient gross tumor resection of glioblastoma, particularly in a high population density country like India.

[008] To overcome aforesaid drawbacks in existing devices, a handy, cost- effective, user-friendly, portable apparatus is proposed herein. Further, the proposed device is intended to detect all types of malignant tumors.

SUMMARY OF INVENTION:

[009] It is an obj ect of the invention to address the issues pertaining to the existing devices for detection of malignant tumors.

[010] It is another object of the present invention to describe a handy, low cost, user-friendly, portable apparatus for detection of malignant tumors.

[Oi l] It is a primary object of the invention to disclose a handy, low cost, user- friendly, portable apparatus by focusing appropriately the desired area of the cells for quick & efficient detection of malignant tumors.

[012] The said apparatus primarily comprises of a head assembly having multiple degrees of freedom; a base; and a flexible connecting body that joins the head assembly and the base.

[013] In an embodiment, the head assembly comprises of a primary light assembly, a secondary light assemblyman image capturing device, an interactive display, and a lens assembly.

[014] In an embodiment, the primary light assembly is configured to emit light of a particular wavelength and to programmable vary intensity of light illumination in small amounts on the region of interest. The primary light assembly comprises of plurality of light components configured to vary intensity of emitted light through a programmable controller. The light intensity of the light components may be varied through interactive display by the user, wherein the intensity suitably varies according to the requirement. The primary light assembly includes plurality of light components having wavelength ranging from 470 - 490 nm. The light components may be LEDs or incandescent lights.

[015] In an embodiment, the apparatus is adapted as a fluorescein guided device. The apparatus provides a sufficient light with sufficient frequency and intensity to fluorescein dyed region of interest in order to affected cells to glow which will help to detect malignant tumor.

[016] In an embodiment, the secondary light assembly is adapted for providing focused light on the region of interest. The secondary light assembly is provided with a flexible attachment, preferably a gooseneck type attachment. The secondary light assembly is composed of plurality of light components whose wavelength falls in the range of 470 - 490 nm. The secondary light assembly is adapted to provide finer focus on the region of interest if the primary light assembly is not sufficient to provide excitation of the cells in the region of interest. In an embodiment, the secondary light assembly is detachable from the main apparatus itself.

[017] In an embodiment, the image capturing device is provided to capture and store still as well as live images of the region of interest. The image capturing device may be selected from any instrument which is capable of capturing and storing still images as well as video.

[018] In an embodiment, the interactive display is connectively coupled to the primary light assembly and the image capturing device. The interactive display is adapted to display images captured from the image capturing device. Further, the user may be able to finely vary the light intensity emitted by the primary light assembly by means of the interactive display. [019] In an embodiment, the lens assembly comprises of at least one plano-convex lens and a fdter. The filter is a long pass interference filter adapted to allow frequencies of more than or equal to 520 nm. Further, a slider mechanism is provided to move the filter towards or away from the image capturing device.

[020] The apparatus is further provided with a communication interface is provided to communicate with external devices.

[021] In an embodiment, the apparatus may also be adapted to be mounted on any platform.

[022] In another embodiment, the apparatus may be a wearable apparatus, adapted to be fit onto a head of a user. Further, the apparatus may be a handheld device, which may include wristwom device.

[023] The apparatus is most suitable for the purpose of deciding site of corticectomy, differentiating the tumor margins from the gliotic brain intraoperatively, achieving gross total resection of tumor. However, the apparatus of the present invention is not restricted to a particular type of a tumor and the scope of the invention may be expanded to any type of tumor, such as gastrointestinal, hepatobiliary, head and neck malignant tumors.

[024] The present invention discloses a method of operation of the apparatus, which comprises: focusing a primary light assembly on the region of interest; viewing and capturing still as well live images through an image capturing device; and displaying the captured images on an interactive display.

[025] The present invention further discloses a method of detecting malignant tumor by employing a handy, low cost, user-friendly, portable apparatus. The method of detection comprises of preoperatively administering fluorescein sodium in a subject; illuminating region of interest by focusing a primary light assembly on the region of interest; selectively and finely varying intensity of the light emitted by the primary light assembly through an interactive display; viewing and capturing still as well live images through an image capturing device; and displaying the captured images on the interactive display, further observing the region of interest through the lens filter assembly. The step of focusing the primary light assembly on the region of interest includes varying intensity of the incident light on the region of interest through the interactive display.

BRIEF DESCRIPTION OF DRAWINGS:

[026] Following figures illustrate the various embodiments of the present invention.

Figure Irepresents front view of the apparatus, in which a head of the apparatus is seen.

Figure 2 illustrates rear view of the apparatus.

Figure 3 illustrates a side view of the apparatus, wherein degrees of movement of the head is illustrated.

Figure 4 illustrates another view of the apparatus.

Figure 5 illustrates the lens assembly comprising the lens (3) & the filter (4). Figure 6 illustrates the secondary light assembly (6).

DETAILED DESCRIPTION OF DRAWINGS:

[027] The following description describes a handy, low cost, user-friendly, portable apparatus for detection of cancer cells. Certain terms and expressions should be construed with their usual meanings. The terms used herein are commonly used in medical as well as engineering fields. Still, some of the expressions are explained herein to avoid any ambiguity, which may arise while referring to the specifications.

[028] “High grade Glioma” is a type of cancer that quickly and, at times, fatally spreads in brain or spinal cord. Fluorescence based detection of glioblastoma is discussed in the Background & Prior Art. The meaning and origin of the term Fluorescein Sodium is also discussed in Background & Prior Art. The “subject” is an umbrella term and may include any patient to be operated, or a subject of trials etc. It may be noted that the present invention is particularly relates to the apparatus that assists in easy, user-friendly detection of cancerous cells, and not intended to claim method of detection per se. Therefore, the present invention should not be misunderstood to be claiming a surgical, or therapeutic method, and such.

[029] The present invention may be better understood by referring to figures appended at the end of the specification. The figures as well as the description herein illustrate and explain more than one embodiment of the present invention. However, the scope of the present invention is not limited to the figures and associated description, and includes any variation in the described embodiments.

[030] The invention describes a handy, low cost, user-friendly, portable apparatus for detection of malignant tumors. Further, the apparatus is adapted as a fluorescein guided device. Referring to Figure 1 to 6, the apparatus primarily comprises of a head assembly having multiple degrees of freedom; a base; and a flexible connecting body. The head assembly comprises of: a primary light assembly (7) configured to emit light of a particular wavelength and to programmably vary intensity of light illumination in small amounts on a region of interest; a detachable secondary light assembly (6) for providing focused light on the region of interest; an image capturing device (9) to capture and store still as well as live images of the desired area; an interactive display (2) connectively coupled to the primary light assembly (7) and the image capturing device (9); and a lens assembly having a predefined focal length, magnification and filtration of light.

[031] In a preferred embodiment, the primary light assembly (7) is configured to emit light of a particular wavelength and to programmably vary intensity of light illumination in small amounts on the region of interest. The primary light assembly (7) comprises of plurality of light components configured to vary intensity of emited light through a programmable controller. The light intensity of the light components may be varied through the interactive display (2) by the user, wherein the intensity suitably varies according to the requirement, but sufficient enough to excite the region of interest mixed with fluorescein dye. The primary light assembly (7) includes plurality of light components having wavelength ranging from 470 - 490 nm, which falls in the blue region of the electromagnetic spectrum. The light components may be LEDs or incandescent lights.

[032] In a preferred embodiment, the apparatus is adapted as a fluorescein guided device. The apparatus provides a sufficient light with sufficient frequency and intensity to fluorescein dyed region of interest in order to affected cells to glow which will help to detect malignant tumor.

[033] In an embodiment, the secondary light assembly (6) is adapted for providing focused light on the region of interest. The secondary light assembly (6) is provided with a flexible attachment, preferably a gooseneck type atachment. The secondary light assembly is composed of plurality of light components falling in the blue region of the electromagnetic spectrum, particularly in a range of 470 - 490 nm. The secondary light assembly is adapted to provide finer focus on the region of interest if the primary light assembly is not sufficient to provide excitation of the cells in the region of interest. With the gooseneck type attachment, the secondary light assembly may be turned into the desired direction for beter viewing of the region of interest. In a preferred embodiment, the secondary light assembly is detachable from the main apparatus itself. The secondary light assembly (6) comprises of at least a pair of light sources (8) having high intensity focus light.

[034] In a preferred embodiment, the image capturing device (9) is provided to capture and store still as well as live images of the region of interest. The image capturing device may be selected from any instrument which is capable of capturing and storing still images as well as video. [035] In a preferred embodiment, the interactive display (2) is connectively coupled to the primary light assembly (7) and the image capturing device (9). The interactive display (2) is adapted to display images captured from the image capturing device (9). Further, the user may be able to finely vary the light intensity of emitted light by the primary light assembly (7) by means of the interactive display (2). The fine variation of the light intensity is effected by a programmable controller by pulse width modulation (PWM) technique. Such method allows smooth variation in the light intensity, a crucial factor for excitation of the fluorescein dye.

[036] In an embodiment, the lens assembly comprises of at least one plano-convex lens (3) and a filter (4). The lens assembly is provided for direct viewing of the region of interest without the image capturing device. Further, multiple people may view the region of interest through the lens assembly. The filter (4) is a long pass interference filter adapted to allow frequencies of more than or equal to 520 nm. Further, a slider mechanism is provided to move the filter towards or away from the image capturing device.

[037] The apparatus is further provided with a communication interface (5) is provided to communicatively couple with external devices. Further, the apparatus is configured to connect with external devices over internet, wired or wireless. With such a facility, still or live images of the region of interest may be shared with external devices for various medical purposes.

[038] As may be seen from Figures 1 - 6, the apparatus may be a platform mounted apparatus in a preferred embodiment. In other embodiment, it may be a wearable apparatus. In a platform mounted embodiment, the apparatus may be erected on any flat surface.

[039] In an alternate embodiment, the apparatus may be a wearable one, which may be worn on the user’s head. [040] The present invention further discloses a method of detecting malignant tumor. The method of detection comprises of preoperatively administering fluorescein sodium in a subject; illuminating region of interest by focusing a primary light assembly on the region of interest; selectively and finely varying intensity of the light emitted by the primary light assembly through an interactive display; viewing and capturing still as well live images through an image capturing device; and displaying the captured images on the interactive display, further observing the region of interest through the lens filter assembly. The administering fluorescein sodium dye is planned preoperatively in the subjects suitable for its use. Fluorescein sodium 10 % is administered intravenously, approximately 3-4 mg/kg body weight, just priorto skin incision. The dye gets concentrated in the tumor cells which can then be visualized through the lens filter assembly, when excitation takes place. The region of interest may either be visualized directly through the lens filter assembly or may be seen on interactive display. Once the tumor is reached, intermittent use of the device is made to identify and differentiate the tumor from the normal brain. After tumor removal, the final inspection of the tumor cavity is done with the device to aid in gross total resection of the tumor. In case where the blue light from the primary light assembly cannot reach the depths of tumor cavity, we can add the secondary light assembly which has a flexible goose neck so as to direct the blue light in the area of interest.

[041] In another embodiment, the apparatus may be a handheld device, including a wristwom device.

[042] The apparatus is most suitable for following usages: to decide site of corticectomy; to differentiate the tumor margins from the gliotic brain intraoperatively; to achieve gross total resection of tumor. However, the apparatus of the present invention is not restricted to a particular type of a tumor and the scope of the invention may be expanded to any type of tumor, such as gastrointestinal, hepatobiliary, head and neck tumors. [043] The apparatus described above is a low cost, portable and user friendly. The present inventor have found that the cost of existing devices are between 45,000 - 100,000 USD, whereas the estimated cost of the present apparatus is 5,000 USD. Due to such advantages of the apparatus, any medical center can own the apparatus, speeding up the process of detection, diagnosis and treatment.

Claims

We Claim,

1. A handy, low cost, user-friendly, portable apparatus (1) for detection of malignant tumors comprising: a head assembly having multiple degrees of freedom; a base; and a flexible connecting body, wherein the head assembly comprises of: a primary light assembly (7) configured to emit light of a particular wavelength and to programmably vary intensity of light illumination in small amounts on a region of interest; a detachable secondary light assembly (6) for providing focused light on the region of interest; an image capturing device (9) to capture and store still as well as live images of the desired area; an interactive display (2) connectively coupled to the primary light assembly (7) and the image capturing device (9); and a lens assembly having a pre-defined focal length, magnification and filtration of light.

2. The apparatus as claimed in Claim 1, wherein the primary light assembly (7) comprises of plurality of light components configured to vary intensity of emitted light through a programmable controller.

3. The apparatus as claimed in Claim 1, wherein the light intensity of the primary light assembly (7) is varied by pulse width modulation (PWM) technique.

4. The apparatus as claimed in Claim 1, wherein the intensity of the light source is primary light assembly (7) is finely varied through the interactive display (2).

5. The apparatus as claimed in Claim 1, wherein the plurality of light sources are of wavelength ranging from 470 - 490 nm.

6. The apparatus as claimed in Claim 2, wherein the plurality of light sources are selected from incandescent light, LEDs.

7. The apparatus as claimed in Claim 1, wherein the secondary light assembly (6) comprises of at least a pair of light sources (8) having high intensity focus light.

8. The apparatus as claimed in Claim 1, wherein the secondary light assembly (6) is provided with a flexible attachment.

9. The apparatus as claimed in Claim 1, wherein the interactive display (2) is a user interface adapted to display as well as communicate with the primary light assembly (7).

10. The apparatus as claimed in Claim 1, wherein the interactive display (2) is selected from LCD, LED or any other human machine interactive display.

11. The apparatus as claimed in Claim 1, wherein a communication interface (5) is provided to communicatively couple with external devices.

12. The apparatus as claimed in Claim 1, wherein the lens assembly comprises of at least one plano-convex lens (3) and a fdter (4).

13. The apparatus as claimed in Claim 12, wherein the filter (4) is a long pass interference filter adapted to allow frequencies of more than or equal to 520 nm.

14. The apparatus as claimed in Claim 12, wherein a slider mechanism is provided to move the filter (4) towards or away from the image capturing device (9). 14

15. The apparatus as claimed in Claim 1, wherein the apparatus is configured to connect with external devices through wired or wireless internet.

16. A method of detection of malignant tumors comprising: preoperatively administering fluorescein sodium in a subject; illuminating region of interest by focusing a primary light assembly on the region of interest; selectively and finely varying intensity of the light emitted by the primary light assembly through an interactive display; viewing and capturing still as well live images through an image capturing device; and displaying the captured images on the interactive display, further observing the region of interest through the lens filter assembly.