Supersonic shear imaging (SSI) is a new ultrasound-based technique for real-time visualization of soft tissue viscoelastic properties. Using ultrasonic focused beams, it is possible to remotely generate mechanical vibration sources radiating low-frequency, shear waves inside tissues. Relying on this concept, SSI proposes to create such a source and make it move at a supersonic speed. In analogy with the "sonic boom" created by a supersonic aircraft, the resulting shear waves will interfere constructively along a Mach cone, creating two intense plane shear waves. These waves propagate through the medium and are progressively distorted by tissue heterogeneities. An ultrafast scanner prototype is able to both generate this supersonic source and image (5000 frames/s) the propagation of the resulting shear waves. Using inversion algorithms, the shear elasticity of medium can be mapped quantitatively from this propagation movie. The SSI enables tissue elasticity mapping in less than 20 ms, even in strongly viscous medium like breast. Modalities such as shear compounding are implementable by tilting shear waves in different directions and improving the elasticity estimation. Results validating SSI in heterogeneous phantoms are presented. The first in vivo investigations made on healthy volunteers emphasize the potential clinical applicability of SSI for breast cancer detection.

Supersonic shear imaging: a new technique for soft tissue elasticity mapping

Diabetic neuropathies are the most prevalent chronic complications of diabetes. This heterogeneous group of conditions affects different parts of the nervous system and presents with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons: 

1. Diabetic neuropathy is a diagnosis of exclusion. Nondiabetic neuropathies may be present in patients with diabetes and may be treatable by specific measures.

2. A number of treatment options exist for symptomatic diabetic neuropathy.

3. Up to 50% of diabetic peripheral neuropathies may be asymptomatic. If not recognized and if preventive foot care is not implemented, patients are at risk for injuries to their insensate feet.

4. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life.

Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are by far the most studied (1–4). There are several atypical forms of diabetic neuropathy as well (1–4). Patients with prediabetes may also develop neuropathies that are similar to diabetic neuropathies (5–10). Table 1 provides a comprehensive classification scheme for the diabetic neuropathies.

View this table:

Table 1 
Classification for diabetic neuropathies



Due to a lack of treatments that target the underlying nerve damage, prevention is the key component of diabetes care. Screening for symptoms and signs of diabetic neuropathy is also critical in clinical practice, as it may detect the earliest stages of neuropathy, enabling early intervention. Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice. The strongest available evidence regarding treatment pertains to these forms.

This Position Statement is based on several recent technical reviews, to which the reader is referred for detailed discussion …

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Diabetic Neuropathy: A Position Statement by the American Diabetes Association

T1, T2, and magnetization transfer (MT) measurements were performed in vitro at 3 T and 37 degrees C on a variety of tissues: mouse liver, muscle, and heart; rat spinal cord and kidney; bovine optic nerve, cartilage, and white and gray matter; and human blood. The MR parameters were compared to those at 1.5 T. As expected, the T2 relaxation time constants and quantitative MT parameters (MT exchange rate, R, macromolecular pool fraction, M0B, and macromolecular T2 relaxation time, T2B) at 3 T were similar to those at 1.5 T. The T1 relaxation time values, however, for all measured tissues increased significantly with field strength. Consequently, the phenomenological MT parameter, magnetization transfer ratio, MTR, was lower by approximately 2 to 10%. Collectively, these results provide a useful reference for optimization of pulse sequence parameters for MRI at 3 T.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.20605

T1, T2 relaxation and magnetization transfer in tissue at 3T

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

Ulcerative colitis and Crohn’s disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn’s and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn’s disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn’s disease, including patients, their families and friends.

https://gut.bmj.com/content/gutjnl/68/Suppl_3/s1.full.pdf

British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults

Shear wave elasticity imaging (SWEI) is a new approach to imaging and characterizing tissue structures based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. SWEI provides the physician with a virtual "finger" to probe the elasticity of the internal regions of the body. In SWEI, compared to other approaches in elasticity imaging, the induced strain in the tissue can be highly localized, because the remotely induced shear waves are attenuated fully within a very limited area of tissue in the vicinity of the focal point of a focused ultrasound beam. SWEI may add a new quality to conventional ultrasonic imaging or magnetic resonance imaging. Adding shear elasticity data ("palpation information") by superimposing color-coded elasticity data over ultrasonic or magnetic resonance images may enable better differentiation of tissues and further enhance diagnosis. This article presents a physical and mathematical basis of SWEI with some experimental results of pilot studies proving feasibility of this new ultrasonic technology. A theoretical model of shear oscillations in soft biological tissue remotely induced by the radiation force of focused ultrasound is described. Experimental studies based on optical and magnetic resonance imaging detection of these shear waves are presented. Recorded spatial and temporal profiles of propagating shear waves fully confirm the results of mathematical modeling. Finally, the safety of the SWEI method is discussed, and it is shown that typical ultrasonic exposure of SWEI is significantly below the threshold of damaging effects of focused ultrasound.

Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics

Magnetization transfer contrast (MTC) experiments using off-resonance irradiation have been performed with an agar gel model by systematically varying offset frequency, amplitude of the RF irradiation and gel concentration. The experimental results are shown to be quantitatively modelled by a two-pool system consisting of a liquid pool with a Lorentzian line shape and a small semisolid pool with a Gaussian lineshape. The fitted model yields physically realistic fundamental parameters with a T2 of the semisolid pool of 13 microseconds. Further analysis shows that the off-resonance irradiation MTC experiment had significant limitations in its ability to saturate the semisolid pool without directly affecting the liquid component.

Quantitative interpretation of magnetization transfer

The institutional review board approved this HIPAA-compliant study. After all five patients with nonalcoholic fatty liver disease signed a consent, they underwent magnetic resonance (MR) imaging for hepatic fat quantification. The purpose of this study was to develop a fast and accurate method to acquire and display quantitative maps of the percentage of hepatic fat. In-phase and out-of-phase gradient-echo MR imaging was performed with dual flip angles (70°, 20°) to resolve ambiguity of the dominant constituent. T2* corrections were also estimated and applied to generate color-coded maps of the estimated percentage of hepatic fat. MR imaging results were compared with biopsy results in two of five patients, and the technique was validated qualitatively and quantitatively with a water-oil phantom. Results of the phantom study confirmed that the dual–flip angle algorithm can be used to correctly identify the dominant constituent, allowing depiction of 0%–100% of fat content. The estimated liver fat fraction...

Hepatic fat fraction: MR imaging for quantitative measurement and display--early experience.

Non-invasive diagnosis and detection of early-stage tumorsis regarded as one of the current challenges in the biomedicalsciences. Magnetic resonance (MR) imaging is a powerful,non-invasive imaging technique because of its high spatialresolution and tomographic capabilities. However, the signalsensitivity of MR imaging for speciﬁc biological targets islargelydependentonthespeciﬁcityandselectivityoftheligandused to target magnetic nanoparticles (NPs) to speciﬁc tissues.Development of tumor-targeted magnetic NPs is necessary toenhance the MR signal sensitivity for in-vivo tumor detection.Variousproteinssuchastransferrin,

/pdf/dendrimer-functionalized-shell-crosslinked-iron-oxide-2l4ok75sb7.pdf

Dendrimer‐Functionalized Shell‐crosslinked Iron Oxide Nanoparticles for In‐Vivo Magnetic Resonance Imaging of Tumors

We demonstrated a unique approach that combines a layer-by-layer (LbL) self-assembly method with dendrimer chemistry to functionalize Fe3O4 nanoparticles (NPs) for specific targeting and imaging of cancer cells. In this approach, positively charged Fe3O4 NPs (8.4 nm in diameter) synthesized by controlled co-precipitation of FeII and FeIII ions were modified with a bilayer composed of polystyrene sulfonate sodium salt and folic acid (FA)- and fluorescein isothiocyanate (FI)-functionalized poly(amidoamine) dendrimers of generation 5 (G5.NH2-FI-FA) through electrostatic LbL assembly, followed by an acetylation reaction to neutralize the remaining surface amine groups of G5 dendrimers. Combined flow cytometry, confocal microscopy, transmission electron microscopy, and magnetic resonance imaging studies show that Fe3O4/PSS/G5.NHAc-FI-FA NPs can specifically target cancer cells overexpressing FA receptors. The present approach to functionalizing Fe3O4 NPs opens a new avenue to fabricating various NPs for numerous biological sensing and therapeutic applications.

Scott D. Swanson

Papers

Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics

Quantitative interpretation of magnetization transfer

Hepatic fat fraction: MR imaging for quantitative measurement and display--early experience.

Dendrimer‐Functionalized Shell‐crosslinked Iron Oxide Nanoparticles for In‐Vivo Magnetic Resonance Imaging of Tumors

Dendrimer-Functionalized Iron Oxide Nanoparticles for Specific Targeting and Imaging of Cancer Cells†