Super-resolution and Speckle Removal in Ultrasonography

Patent Filing No. 1296/KOL/2010, PCT application No. PCT/IN2011/000789, Countries filed: USA, South Korea: An improved ultrasound imaging method/technique for speckle reduction/suppression in an improved ultra sound imaging system

Patent Filing No: 636/KOL/2010: Super-resolution on Polar Domain Data

Award won

One of the Top 50 technologies of DST Lockheed Martin India Innovation Growth Program Award 2015

Background

First picture of most babies is captured before their birth using ultrasound (US) imaging. However, US imaging lacks spatial resolution and suffers from multiplicative nature of speckle noise. Newer technologies require more hardware that drives the cost but does not increase the image quality in the depth of the body. Our invention using super resolution (SR) and novel speckle removal algorithm improves image quality and increases operating depth of imaging with a minimal increment in cost. Rural India (>6 lakh villages) provides a big market to exploit the benefit of low cost SR enhanced US system with reduction in maternal mortality rate and improving surgical outcomes. Estimated reduction in cost would be at least 70-80% in comparison with a more hardware intensive equipment.

Technical summary

Ultrasound is safest, most inexpensive and highly portable method of imaging making it first line of imaging in most clinical conditions. However, it is characterized by low resolution as compared to other imaging techniques. Also, depth of penetration decreases with increase in operating frequency. We have invented novel speckle removal algorithm which together with super-resolution technique helps to significantly enhance resolution and operating depth of ultrasound imaging. These improvements make even subtle changes in diseased conditions more visible for better clinical diagnosis. Our invention does not need significant change in ultrasound equipment hardware (sensors and signal processing).  Therefore our invention provides better image quality at no added cost.

Advantages 

- Innovation is related to design and fabrication of Ultrasound Imaging System.

- Using multiple images taken by low cost hardware Super Resolution technique. can produce better quality image

- Combining scan conversion with post processing helps to get better speckle noise suppression with lower computation.

- Only a modest increase in computation capability resulting in better image means reduction of Ultrasound imaging system

- Areas of the body with low motion, e.g. abdomen, neonatal brain, musculoskeletal, etc. are ideal for such imaging.

- Increase in image quality helps to increase the operating depth of the Ultrasound imaging systems.

Commercial applications

SR enhanced US systems have large market potential due to significant reduction in cost. US equipment market will be $6.2 billion by 2019. 2-D US imaging is 50% of existing market. Assuming SR forms 5% of 2-D US imaging equipment value, the market potential for our product is $0.15M. If we captured 10% of 2-D US market share by 2019, estimated market value for product would be $150,000 per year. Algorithms for SR have been developed and have been tested with US simulator and now it should be integrated with US equipment for clinical efficacy before selling.

Paper-Pencil based Diagnostic Kit

Patent Filing No. 701/KOL/2015

Title: A ‘paper-and-pencil’-based diagnostic kit for ready and simultaneous detection of one or multiple analytes

Brief Description

This invention illustrates the use of ‘paper-and-pencil’ based diagnostic device for rapid and simultaneous detection of one or multiple analytes. Fluid transportation is guided by the hydrophobic barriers which have been fabricated by following a simple printing-based methodology. External electric field is applied for fast and controlled transport of the fluid, while the electrodes have been fabricated by sketching the graphite tip of a pencil on paper surfaces. Application of external electrical actuation between sample source and test regions enhances the flow rate of the sample fluid to the test regions due to the combined  capillarity and electrokinetic effect; and thus reduces the diagnosis time. The detection  is performed following a colorimetric approach, where the colorimetric signals are generated due to the chemical reaction between the pre-embedded reagents on the detection pads and sample fluid.

Advantages:

- Inexpensive

- Minimum resource is required

- Easy fabrication and  mass fabrication is possible

- Fast and on-spot diagnosis

- Portable in nature and  no special expertise is needed for operating the device

Commercial Applications:

Point-of-care diagnostics, Analytical laboratories, Diagnostics laboratories, and for Food and Water quality control

Bone Grafts via Bio-mimetic Approach

Patent Filing No.: 983/KOL/2014

Award won
DST Lockheed Martin India Innovation Growth Program Award 2015


Brief description

Healing of complicated bone fractures, fibrous non-unions and severe trauma require additional support material as template to aid the healing process. Material selection and template design depend on physico-mechanical properties of bone/tissues and their regeneration kinetics. Calcium phosphate (CaP) based hybrid composite with non-collagenous polymer (NCP) scaffold becomes a promising approach for bone graft replacement due its structural and functional characteristics relevant to musculoskeletal tissue.

 The present invention relates to compositional aspect, fabrication strategies and three dimensional architectural designs towards skeletal tissue healing. Specifically, synthesis procedure of mono/multiphasic calcium phosphates from biological wastes, phosphorylation of polymers, their applications individually or in combinations towards repairing/regeneration of skeletal tissues and other biomedical means. Besides bioactivity, this hybrid composite containing inorganic phase will offer high elasticity and organic matrix will provide resilience and resistance to failure. Therefore depending on the tissue type, mineral to organic ratio can be altered to match the tissue specific physico-chemical properties. CaP based composite scaffold with phosphorylated polymers have pH buffering effect which control degradation and resorption rate of polymer as well as suppress consecutive acidic degradation. Not only combination of two different phases, but also their organization can be varied with analogues to the bone in terms of pore architecture by various scaffold design approaches. Both the ceramic phase and polymer phase are originated from biological waste material, transformed in to biologically active/relevant material in a cost effective way.

Summary of the technical details

Resorbable, multi-scalar hierarchical, hybrid composite bone graft has been made, comprising of: (a.) an inorganic phase of multiphasic calcium phosphate (CaP) and its derivative thereof, it is biocompatible, osteoconductive, osteoinductive, with plurality of highly interconnected multi-scalar pores. It is synthesized from biological waste materials (egg shells, sea shells, etc.) in a cost effective single step sintering process. It is highly interconnected, microstructural scaffold in the form of 3D printed, fibrous patterned, foam and as spacer. (b.) a second material is a natural origin resorbable functionalized polymer (phosphorylated chitosan and its derivative) or polymer selected from the group comprising polylactic acids, polyglycolic acids, and combinations thereof. Functionalized chitosan synthesized in a novel, time saving, cost effective, microwave irradiator method. Polymer phase fabricated in the form of nanofibrous film, microfilm, fibrous, 3D printed and spacer.

Combination of two phases and their organization varied with analogues to the targeted bone in terms of microstructure and physico-mechanical properties. 

Advantages of this technology

(1)   Innovation is related to design and fabrication of composite scaffold via combinatorial approach towards bone regeneration. 

(2)   Customized bone graft prepared in minimal processing steps with cost effective method.

(3)   Raw materials for both the phases are natural origin and biological waste.

(4)   Combination of two different phases and their organization can be varied with analogues to the targeted bone.

(5)   Composite scaffolds have nano-micro architecture with bone like structural hierarchy.

(6)   Prepared scaffold is bioactive, resorbable, osteoinductive and osteogenic.

Commercial aspects of the technology & Industries benefiting from it

Every year, 5.8 million people die from orthopaedic trauma and related injuries, 95% of these deaths occurring in developing countries. Being a highly populous developing nation, India faces the brunt of orthopaedic related disease and injuries. Moreover, India spends only 4% of its GDP on healthcare sector, which is insufficient. On the other hand, the currently available bone implants are highly expensive and mostly imported. Therefore, in such low resource settings, we need to come up with alternative solutions, that are affordable and equally or more effective. Current available options are slow in healing, required revision surgeries that cause several associated complications as well.

In this context, we have come up with a ‘HYBRID BONE GRAFT’ as bone substitute implant from natural origin biological waste, having rapid integration with host tissue, results in faster healing, following completely reabsorption and no revision surgeries required. Importantly, it is prepared via minimum processing steps, can be customized and scalable process using biological waste, which makes it around 5-10 times less costly and affordable.

The technology is available off-the-shelf and it can be brought to market with nominal investment.  

 

Noninvasive Photoacoustic Blood Glucose Measurement

Patent Filing No.: 670/KOL/2013

Award won:
1. 2nd Prize of USD 10,000 in Healthcare Innovation World Cup 2013 at New York, USA
2. DST-Lockheed Martin India Innovation Growth Program Award 2015

Background:
Diabetes is a highly prevalent disease with an estimated 387 million people suffering from it worldwide. Defects in insulin secretion and action prevent cells from taking up glucose from blood leading to hyperglycemia, i.e., high blood glucose levels, which results in a host of micro- and macro- vascular complications such as impaired vision and renal function. Large scale randomizedcontrolled
trials have shown that tight glycemic control with multiple glucose measurements and intensive insulin therapy leads to delayed onset and progression of complications, making it an important element of diabetes care. A continuous, non-invasive blood glucose monitoring system based on photoacoustic spectroscopy is proposed for diabetes care.

Brief description:
Present state-of-the-art glucose monitors require patients to lance their fingers and test drops of blood using electrochemical testing strips multiple times each day. The pain and discomfort associated with the procedure often leads to non-compliance and irregular testing, resulting in poorer treatment outcomes. The repetitive costs associated with the one-time use testing strips also prevent wide scale use in developing nations where healthcare costs could take up a major portion of household income. In addition, current methods are labour intensive and time consuming to implement frequently and yield discontinuous measurements. Non-invasive glucose monitoring based on photoacoustic spectroscopy offers painless measurement in a continuous manner allowing for better treatment outcomes. Continuous measurements would also allow for easier detection of hyper- and hypo- glycemic events, which might otherwise be missed when only two or three glucose measurements are made each day. This ultimately reduces the risk of complications associated with diabetes, leading to efficient diabetes management and lower healthcare costs.

Technical details:
The photoacoustic effect involves excitation of a sample by short duration intense pulses of electromagnetic radiation, such as a laser, leading to optical absorption followed by non-radiative heat release and thermoelastic expansion. In absence of excitation, this leads to the generation of a pressure wave in the sample. The generated pressure is proportional to the sample optical properties and is used to predict the sample constituent concentration. Blood glucose concentration is measured by selecting excitation wavelengths that are primarily absorbed by glucose molecules present in the
tissue. Glucose also affects the physical properties of the sample leading to changes in the sample photoacoustic response.

The measurement system consists of a pulsed laser diode which provides electromagnetic excitation, a piezoelectric transducer for measuring the generated pressure wave, and associated signal processing units. The photoacoustic signal obtained at the transducer output is amplified and processed to remove noise. The noise free signal is processed further and calibrated to obtain a glucose value. Trends in glucose concentration can be used by the diabetic to manage daily medication, nutrition, and exercise, and can be sent to a doctor periodically for follow up investigations. The signal processing, storage, and calibration can be done on a smart phone and the results can be continually updated to a central server for use.

The technique was initially validated in vitro on glucose solutions. Simulations performed to check variation in the photoacoustic response with glucose concentration were found to correlate with the experimental findings. The photoacoustic signal amplitude is observed to increase with the concentration of the glucose. Following this, in vivo measurements were made on tissue wherein the variation in photoacoustic responses to follow the glucose concentration trends.

Research Team: 
Mr. Praful P. Pai   Mr. Pralay Mandal   Mr. Shib Shankar Das   Mr. Omkar C. Kulkarni   Mr. Pradyut Kr. Sanki   Mr. Satyabrata Sarangi   Prof. Anindya  Sundar Dhar   Prof. Swapna Banerjee

Contrast Agent for Medical Imaging

Patent Filing No.: 566/KOL/2013

Award won
1. BIRAC-SRISTI Gandhian Young Technological Innovation Award, 2015
2. DST-Lockheed Martin India Innovation Growth Programme Award 2015

Brief description
A medical contrast agent is a substance used to enhance the visibility of internal body structures for clinical diagnosis. It is commonly used to enhance the visibility of gastrointestinal tract to detect numerous disorders like hernia, inflammation, bleeding, blockages and cancer and so on. The present state of art includes swallowing contrast agent, followed by their imaging via X-rays. However, all current contrast agents are non biocompatible and are difficult to swallow. In this regard, we have developed biocompatible, non-toxic, contrast agent that facilitates accurate medical imaging.

Summary of the technical details

Herein we propose a novel radiopaque derivative that is easily detectable with the X-ray radiography, fluoroscopy and CT.  The product consists of iodine, a crosslinker and a polymer with amine linkages. The derivative is biocompatible as well as biodegradable as it is made of materials of natural origin. Additionally the derivative could be fabricated to form micro or nano beads for various gastrointestinal tract imaging applications. 

Advantages of this technology

·           Low cost product developed by the use of eco-friendly and biodegradable materials

·         Simple technology that do not need high technical expertise.

·         Is compatible with the present X-ray imaging techniques.

·         Real Time monitoring of gastrointestinal tract

·         Post operative non-invasive assessments of the implants for fast clinical decisions

·         Product offers antibacterial property

Commercial aspects of the technology

Since, the starting materials are cheap and the process involves only one step reaction, the cost of manufacturing the product is low. Taking the channel cost and the cost to launch the product in the market, our product pricing is comparable to the existing products in the market. Our target customers are corporate/govt hospitals, radiology labs, diagnostic centre and individual doctors whereas our users are patients suffering from gastrointestinal disorders.

The technology can be brought to market with minimum investment.