Minimally Invasive Focused Ultrasound (MIFUS) for Brain Surgery

Abstract

HIFU (High-Intensity Focused Ultrasound) sometimes FUS or MIFUS is a highly precise medical procedure using high-intensity focused ultrasound to heat and destroy pathogenic tissue rapidly in the brain for neurosurgical purposes, by causing coagulation necrosis. Here we have described a system that uses specially designed micro-transducer heads that are placed inside the later ventricles for the purposes of MIFUS lesioning of brain targets under real time MRI, endoscopic and Doppler guidance. A minimally invasive approach using Kocher's point allows small incisions with little bleeding, recovery time, infection risk and surgical time. This approach allows insertion of the micro-ultrasound transducers into the lateral ventricles of the brain avoiding skull bone attenuation of the ultrasonic waves and unnecessary heating of brain tissues in the process.

Claims

1. A system comprising: a. an entry port sheath defined as a 3 mm mesh tube which can be expanded up to 1.2-1.5 cm diameter and is used as a port of entry once the burr holes and ventricle tap have been finished, the port being set in a fiberoptic tube having have UV light transmitted intermittently or continuously therein; b. Micro-transducer ultrasound heads having a size between 1 and 5 mm and c. a computer configured to calculate an assembly plan program, a component program for calculation of transducer number, and real time ventricular video images guiding plan operation in real time.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0122] FIG. 1 Image of difficult to avoid brain vasculature. This figure illustrates the potential difficulty in targeting a point in the brain.

[0123] FIG. 2 Kocher's Point Illustration. This figure shows the approximate position of the point on a patient's skull where the expandable sheath will be inserted.

[0124] FIG. 3 The MIFUS Overall Configuration. This is a system diagram of all of the major pieces of the MIFUS system and their basic connectivity.

[0125] FIG. 4 Relevant Areas of the Brain. The ventricular position in the brain that will be used is illustrated here.

[0126] FIG. 5 Micro Transducer (Zoom View) Construction. This figure shows a typical assembly of micro transducers at the far end of the expandable sheath after the sheath has been inserted into the brain of the patient.

[0127] FIG. 6 MRI/Patient Positioning Relationship. This shows how the patient will be placed on the MRI table in a stable position; and how adjustments can be made to the equipment if necessary.

[0128] FIG. 7 MRI Possible Configurations. Shown here is a possible position that the patient may have on the MRI table other than flat on the back.

[0129] FIG. 8 Kocher's Point Restraining Bolt. This illustrates the type of stabilization that will be used to hold the expandable sheath and associated wiring that goes through the sheath.

[0130] FIG. 9 Ventricular Equipment View. This figure gives a symbolic view (not to scale) of the components of MIFUS utilized inside the brain.

[0131] FIG. 10 Lesioning of Brain Tumor View. This figure is a variation of FIG. 9 which shows how the ultrasound waves will be focused on a brain tumor; and it shows how the Doppler ultrasound will be located to transmit positioning information to the computer.

DETAILED DECSRIPTION OF EMBODIMENTS

[0132] Embodiments of the present invention relate to systems, methods and kits for heating targets in the brain using high intensity focused ultrasound fired from transducer heads placed inside the brains lateral ventricles using a minimally invasive approach all while under the real time imaging control of MRI, Doppler and visual systems.

[0133] The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the exemplary system only and are presented in the cause of providing what is believed to be a useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how several forms of the invention may be embodied in practice and how to make and use the embodiments.

[0134] For brevity, some explicit combinations of various features are not explicitly illustrated in the figures and/or described. It is now disclosed that any combination of the method or device features disclosed herein can be combined in any mannerincluding any combination of featuresany combination of features can be included in any embodiment and/or omitted from any embodiments.

[0135] In relation to the figures the following numbers indicate:

[0136] 1Kocher's surgical entry point

[0137] 2Expandable sheath

[0138] 3Brain parenchyma

[0139] 4Lateral ventricle

[0140] 5Expandable sheath with ultrasound probe

[0141] 6Ultrasound transducer head

[0142] 7Example of brain tumor target

[0143] 8Control computer and software

[0144] 9Relevant brain anatomy with ventricular system displayed inside

[0145] 10Example of disassembled transducer head parts that fit together inside

[0146] 11Example of assembled transducer which is movable in 3D inside the ventricle

[0147] 12MRI with device during MIFUS neurosurgery; one possible configuration

[0148] 13Cross section of MRI with patient during MIFUS neurosurgery

[0149] 14Skull Bone

[0150] 15Brain parenchyma exposed through a burr hole created in skull

[0151] 16Restraining bold frameless system

[0152] 17Top tube of restraining bold can be longer than implied by this simple drawing as needed for MIFUS instruments stability

[0153] 18One possible configuration of MIFUS instruments inserted for neurosurgery

[0154] 19One possible configuration of MIFUS instruments positioned in brain for surgery while connected to MRI and computer

[0155] This device is called Minimally Invasive Focused Ultrasound (MIFUS) for brain and it is a system of components that will take advantage of proven capabilities for such things as tumor ablation; but at the same time will utilize the brains lateral ventricle as an anatomical advantage and advanced ultrasound transducer micro technology. MIFUS neurosurgery in this context is defined as follows: [0156] Brain surgery done with only a small incision and through a cannula often employing an endoscope [0157] Little to no risk of bleeding and no damage to eloquent brain tissue; [0158] Sterile hands free environment [0159] Very brief surgical times as compared to craniotomies.

[0160] The MIFUS concept will depend on placing the ultrasound transmitters inside of the brain rather than outside as shown in FIG. 9. Earlier ultrasound technology consisted of transmitters that were too large for MIFUS.

[0161] Furthermore, the surgical configuration will have the following features: [0162] Utilize surgical and physical anatomy with micro-technology to minimize bone removal, and brain and blood vessel collateral damage [0163] Insert a small diameter probe through small hole, created at Kocher's point on the skull, into one or both lateral ventricles, see FIG. 2. [0164] Attach stabilization mechanism to support insertion of the expandable sheath, FIG. 8. [0165] Move specially designed micro ultrasound transducer heads through the probe. [0166] The key aspect of the MIFUS system is to use recently available, specially designed micro ultrasound transducers heads having the following specifications: [0167] Very small 1-5 mm or less; [0168] Movable/steerable in 3D; [0169] Can be assembled inside lateral ventricle; [0170] Can be catheter cooled; [0171] Can provide sufficient energy intensity and focal length to reach and safely destroy targets within the brain as shown in FIG. 10. [0172] Use currently available video, MRI and ultrasound for real time positioning, thermal dose delivery control and visual data feedback of transducer action, see FIG. 10. [0173] Complete brain exposure is therefore available to multiple focused ultrasound transducers with one small (12 mm) hole; and [0174] Ratio of exposed brain surface area (targetable) to entry point surface area is extremely high; [0175] No other current technology can achieve this without having to cross a major amount of bone and or destroy vessels and brain.

[0176] Thus, the lateral ventricle (anterior horn) of the brain is used as a staging point for focused ultrasound. The anatomy of the frontal horn of the lateral ventricle allows device placement with a working ellipsoid volume of 13-15 ml (frontal horn diameter 15 mm51 mm). Interior use of the ultrasound avoids the bone heating problem as depicted in FIG. 4. Interior placement of the transducers also allows safe room to work inside the brain for device assembly as well as allowing targeting of virtually any point in the brain. This approach protects important neural tissue and avoids risk to major blood vessels.

[0177] The MIFUS system is organized into the following three functions. [0178] 1. Targeting, navigation and dose delivery calculations software [0179] 2. Real time visual feedback using MRI and/or Ultrasound [0180] 3. Ultrasound delivery components and software

[0181] Target Patient Population [0182] Potential patients which may benefit from focused ultrasound treatments in brain include: [0183] Brain tumors (pediatric and adult, benign and malignant), see FIG. 1; [0184] Metastasis to brain; [0185] Brain abscesses; [0186] Vascular LesionsIntravascular clot lysis in stroke, AVMs, cavernous malformations, telangiectasias; [0187] Deep brain stimulation targets (STN and BG targets); [0188] Epilepsy (medically refractory); [0189] Blood brain barrier disruption for targeted drug delivery (theoretical); [0190] Depression.

[0191] Targeting, Navigation and Dose Delivery Calculations Software

[0192] The MIFUS computer software will accomplish the following functions as shown in FIG. 3: [0193] Planning software for probe navigation, for transducer(s) positioning and stabilization inside skull [0194] Assembly plan program calculates most efficient plan [0195] Calculation of transducer number and other needed surgical elements (pre-surgical planning) [0196] Real time intraoperative ventricular video images guiding plan and operation in real time using stereotactic approaches [0197] Targeting software for optimally guiding energy to a precise area, or areas, of targets, at precise times, with minimal energy delivery to the surrounding tissue used for: [0198] Navigation softwareDistance from transducer to target [0199] Positioning of heads [0200] Ablation programDepends on blood flow to target, surgeons desires etc. [0201] Determining needed frequency [0202] Ablation monitoring software (all in real time) [0203] Displays color coded temperature map of target [0204] Displays ultrasound and Doppler blood flow to target [0205] Displays color coded map of transducers [0206] Display fused images: MRI anatomy and color coded thermal ablation

[0207] Real Time Visual Feedback

[0208] Visual feedback from inside the brain involves the use of MRI and Doppler ultrasound. Characteristics besides those described above with the aid of the computer are as follows, see FIGS. 3 and 10. [0209] MRI allows real time images of target and transducer, positions, sizes and temperatures [0210] Can account for brain shift, movement of structures and changes in blood flow intraoperatively [0211] Ultrasound allows real time images of target, Doppler blood flow and elasticity (ultrasound elastography) analysis of target vessels

[0212] Focused Ultrasound Delivery Components

[0213] The ultrasound transducers will reside at the distal end of the entry port sheath inside the lateral ventricle anterior horn. The sheath is a 3 mm mesh tube which can be expanded up to 1.2-1.5 cm. An endo scope with optional, fiber optic capability will be inserted to facilitate transducer construction and heads position (1 mm diameter). The sheath is inserted through a small hole in the skull at Kocher's point. The ultrasound transducers have the following characteristics: [0214] Transducer Heads [0215] Multiple heads with pseudo 3D maneuverability; [0216] Can be assembled inside ventricle, see FIG. 5; [0217] Closed loop cooling circuitry; [0218] Very small but powerful enough to provide up to 50 W/cm2 intensity; [0219] MR compatible. [0220] Calculated example field parameters of transducer heads in water with intensity up to 300 W/cm2

TABLE-US-00001 Focal Transducer Focal Length Frequency Diameter Length Max (MHz) (mm) Min (mm) (mm) 2.25 6.35 8.9 11.4 2.25 9.5 12.7 26.9 3.5 6.35 9.8 17.8 3.5 9.5 15.24 41.9 5 6.35 10.9 25.4 5 9.5 15.24 59.7 10 6.35 16.7 53.3 10 9.5 15.24 120.6 15 6.35 12.7 80.0 15 9.5 15.2 180.3 20 6.35 12.7 106.7 20 3.17 6.35 25.4 25 6.35 12.7 133.4

[0221] Combined MIFUS Operative Device Concept (See FIG. 3) [0222] Utilize brain lateral ventricles as staging point for MIFUS along with micro-technology to avoid skull bone attenuation. [0223] Use video, Magnetic Resonance Imaging (MRI) and ultrasound for real time data feedback. [0224] Complete brain exposure to multiple focused ultrasound transducers with one small (12 mm) hole. [0225] Exposed brain (targetable) surface area to entry point surface area to is extremely high [0226] No other current technology can achieve this without having to cross a major amount of bone and or destroy vessels and brain tissue

[0227] Kocher's Point [0228] Utilize unique point on skull for entry [0229] Kocher's point is 2-3 cm lateral to the midline of the skull and 1-2 cm anterior to the coronal suture, see FIG. 2: [0230] Special point which gives a direct line to the lateral ventricle [0231] Positions device in larger area (anterior horn) of the ventricle but also avoids all major blood vessels and eloquent neural strips [0232] Special because it gives a direct line to the lateral ventricle and also avoids all major blood vessels and eloquent neural strips, such as the pre and post central strips [0233] Burr holes, (12 mm) are typically drilled in the bone at this point for a ventriculostomy (bedside procedure) [0234] A 2-3 mm expandable sheath can be inserted into the ventricle and then expanded to some degree even up to 12 mm

[0235] The MIFUS System [0236] Use the lateral ventricle (anterior horn), see FIG. 4, as a staging point for focused ultrasound; [0237] Anatomy of the frontal horn of the lateral ventricle allows device placement with a working ellipsoid volume of 13-15 ml (frontal horn diameter 15 mm51 mm); [0238] Avoids bone problem; [0239] Allows safe room to work inside the brain for device assembly; [0240] Allows targeting of virtually any point in the brain; [0241] Provides a fluid buffer around any potential device; [0242] Protects important neural tissue; [0243] Avoids risk to major blood vessels.

[0244] Relevant Areas of the Brain [0245] Use specially designed mico-transducer heads [0246] Very small 1-5 mm [0247] Movable/steerable in 3D [0248] Can be assembled inside lateral ventricle [0249] Can be catheter cooled [0250] Can provide sufficient energy intensity and focal length to reach and destroy targets

[0251] In FIG. 5, the transducer assembly is illustrated. Three parts of a transducer are assembled as shown ultimately providing a 360 degree movement in 3D. These can be magnetic locking mechanisms, mechanical locking mechanisms, electrical locking mechanisms or an operable combination of all of the above.

[0252] Entry Port Sheath [0253] 3 mm mesh tube which can be expanded up to 1.2-1.5 cm; [0254] Optional, fiber optic scope inserted to facilitate transducer construction and heads position (1 mm diameter).

[0255] Computer [0256] Construction Software (used for transducer assembly inside skull) [0257] Assembly plan program calculates most efficient plan [0258] Calculation of transducer number and other needed surgical elements (pre-surgical planning) [0259] Real time intraoperative ventricular video images guiding plan operation in real time [0260] Targeting Software (guides energy to precise area or areas of target at precise times) used for: [0261] Navigation SoftwareDistance from transducer to target [0262] Positioning of Heads [0263] Ablation programDepends on blood flow to target, surgeons desires etc. [0264] Determining needed frequency [0265] Ablation Monitoring Software (all in real time) [0266] Displays color coded temperature map of target [0267] Displays ultrasound and Doppler blood flow to target [0268] Displays color coded map of transducers [0269] Display fused images: MRI anatomy and color coded thermal ablation

[0270] MRI and Ultrasound (See FIGS. 6 and 7) [0271] MRI allows real time images of target and transducer, positions, sizes and temperatures [0272] Ultrasound allows real time images of target and Doppler blood flow analysis of target vessels

[0273] Problems Solved/Advantages of MIFUS [0274] Benefit from the same focused ultrasound abilities as external transducers without skull bone attenuation problem. [0275] Allow focused ultrasound targeting of any area of the brain with multiple transducer heads in tandem from multiple angles (steerable heads). [0276] SafetyDo not destroy important neural tissue or cause major bleeding [0277] VersatilityUsable for many different indications, multiple lesions per surgery, multiple thermal ablation options, multiple transducer heads placed one or both ventricles. [0278] Procedure relatively inexpensive compared to the surgery and therefore market competitive (no need for long time hospitalization). [0279] Minimally invasive: creates 1 very tiny 12 mm hole in bone, and is hands free. [0280] Avoid major blood vessels and bleeding risk. [0281] Avoids destruction of vital brain tissue. [0282] Avoids radio-therapy of brain tissue. [0283] Allows targeting of multiple lesions in a single procedure (metastasis). [0284] Allows almost any conceivable three dimensional targeting to a lesion, not just a standard head on approach (Radio Frequency, RF, or laser). [0285] Allows independent ablation planning by surgeon tailored to condition. [0286] Keep temperature rise within a very small area. [0287] Minimal healing time for patient.

[0288] Examples of Intended Use [0289] Brain Tumors (including metastasis); [0290] Brain abscesses; [0291] Brain, ventricular and spinal cysts; [0292] Vascular lesions (Arteriovenous malformation, AVMs, cavernous malformations and capillary telangiectasias), clot (stroke), aneurysms; [0293] Part of lesioning for Deep Brain Stimulation, DBS, to treat Parkinson's Disease, PD, essential tremor and epilepsy. [0294] Targeted drug delivery systems

[0295] Summary of MIFUS Advantages [0296] The idea uses new a specially designed device which can deliver high intensity focused ultrasonic waves to virtually any part of the brain with little risk to the patient. The tissue destruction is monitored in real time and controlled in a precise manner. [0297] The device utilizes new engineering technology not yet seen in any current surgical/medical device and takes advantage of anatomical and surgical anatomy to avoid current major problems with brain focused ultrasound [0298] The advantages of this method/device over others are its simplicity, versatility and effectiveness [0299] Its simplicity allows it to be low cost. This cost benefit is realized in terms of low device cost, reduced operation training time and lastly markedly reduced patient recovery/hospitalized time [0300] This device avoids pitfalls of recent or earlier methods which attempted to use focused ultrasound in brain and circumvents many of the issues that made these earlier methods unsuccessful.