What Future for Ultrasound in Medicine?

What comes to mind when asked the question: “Welche Zukunft für Ultraschall in der Medizin” (What Future for Ultrasound in Medicine?)? I guess all of us would think about the editorial policies, publisher’s choices and administrative issues of our beloved journal and might frown. However, at the beginning of the year 2018, the future of the journal is fortunately very bright. It is quite successful and, therefore, the goal of this article is to review some new achievements and exciting future prospects of ultrasound techniques in the various medical fields, including those currently poised to be implemented in daily practice and those that are still only on the distant horizon. We hope readers will be able to discover future ultrasound applications that they are unaware of but may soon have a chance to use. We only regret that this overview will probably seem incomplete due to the limited publication space and the speed of change in these fields.

Cardiology is perhaps the most paradigmatic example of the manifold applications of ultrasound. With improvements in 3 D and 4 D interactive ultrasound techniques, the preoperative workup for transcatheter valve replacement/repair has gained a simple and noninvasive tool [1]. Even more remarkably, 3 D printing companies are showing interest in printing models from ultrasound images, for instance from transesophageal exams, which could help with preoperative planning [2]. 3 D echocardiography is expected to progressively become more integrated into the clinical guidelines and routine practice. Indeed, primary rather than secondary prevention is still the preferred approach in cardiovascular diseases.

With the current obesity epidemic, many developed countries around the world are seeking ways to improve weight loss. Ultrasound might play an unexpected role even in this setting. Researchers from the United States recently described an innovative gene delivery therapy that produces an increase in fat and glucose oxidation and weight loss in diabetic rats, by genetically inducing a brown adipose tissue phenotype. In particular, a gene ‘cocktail’ was delivered into skeletal muscles of Zucker obese diabetic rats via tiny gas-filled microbubbles using ultrasound-targeted microbubble destruction (UTMD) [3]. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal, resulting in the release of DNA and transfection of neighboring cells within the tissue [3].

The therapeutic role of ultrasound has been established in the neurosciences, with focused ultrasound (FUS) having being approved for refractory essential tremor by the Food and Drug Administration (FDA) in 2016 [4]. It is currently under investigation as a possible treatment for disabling dyskinesia in Parkinson’s disease, neuropathic pain, obsessive-compulsive disorder, and epilepsy [4]. Its ability to transiently open the blood-brain barrier in localized brain regions also offers a promising route for targeted drug delivery, potentially leading to novel therapeutic approaches in chemotherapy delivery for brain cancers [5] and in albumin-mediated plaque clearance in Alzheimer’s disease [6]. FUS is not the only example of a medical use of ultrasound beyond mere imaging. Functional assessment might become a further application.

In particular, Ultrasound Optical Tomography (UOT) has recently shown promising results in the assessment of the blood oxygen saturation of deep sites, such as the front side of the myocardial tissue [7]. With sufficient improvement, this technique could provide a real-time noninvasive method to verify suspicion of heart infarction or angina.

The innovations regarding ultrasound techniques are not limited to the aforementioned fields. Ultrasound examination of the oral cavity structures, epiglottis, vocal cords, and subglottic space is becoming increasingly popular among anesthesiologists. The possible applications range from preoperative evaluation (vocal cord palsy or deviation/stenosis of the trachea) to postoperative management of the patient (positioning of endotracheal tube or laryngeal mask placement, navigating tool for emergency cricothyrotomy) [8]. Furthermore, endobronchial ultrasound is currently used for real-time navigated biopsy of pulmonary nodules [8] and is discussed in the current issue of the journal [9].

There are an increasing number of potential ultrasound applications even in a specialty such as dermatology. High-frequency 100 MHz transducers have an axial resolution of 11 μm and a lateral resolution of 30 μm and allow visualization to a depth of 2 mm. Clinical studies in psoriasis have shown very good correlation between ultrasound and histology in the evaluation of psoriatic plaques. Moreover, preliminary findings suggest that ultrasound is also able to capture modifications induced by local treatments, offering multiple new research perspectives [10].

In 2017 EFSUMB published an update of its liver elastography guidelines [11]. Ultrasound elastography has indeed been a revolution in many clinical fields and in hepatology in particular. However, it is still not the ultimate answer regarding all tissue characteristics, as it appears unable to properly distinguish fibrosis from interstitial pressure due to inflammatory edema. Experimental research suggests that refined analysis of ultrasound shear waves is able to produce information about viscoelasticity separate from information regarding fibrosis and stiffness [12]. This technical possibility could open the door to reliable and accurate noninvasive assessment of the many properties of tissues, including the liver.

One of the diseases with the greatest social impact in Western countries is Alzheimer’s disease. Proper and early diagnosis is important from various points of view. Results of a study published in our journal in 2017 suggest that structural transcranial ultrasound is able to visualize and measure the medio-temporal lobe [13] and could possibly constitute a cheap and easy-to-use supplement to other techniques for the diagnosis of Alzheimer’s disease by showing a small medio-temporal lobe. It may be especially useful as a screening tool in the large population of individuals with cognitive decline. Further studies are needed to validate this novel method.

Ultrasound has also been utilized for decades to support interventional procedures, with some of these applications being well established while others are relatively new and gaining popularity, such as vascular catheter guidance or endoscopic ultrasound-guided therapeutic interventions [14] [15].

In conclusion, the imaging potential of ultrasound in medicine is still tumultuously increasing, apparently at a much higher rate than other imaging methods, with a unique role also in therapeutic applications, leading to a definitive “cultural revolution” in the future of ultrasound in medicine. Hence, the future of Ultraschall in der Medizin is sure to be bright from all points of view.

Francesco Tovoli

Vito Cantisani

Cosima Schiavone

Fabio Piscaglia

• References

• 1 Kwon SH, Gopal AS. 3D and 4D Ultrasound: Current Progress and Future Perspectives. Curr Cardiovasc Imaging Rep 2017; 10: 43 doi:10.1007/s12410-017-9440-2
• 2 Mashari A. Making three-dimensional echocardiography more tangible: a workflow for three-dimensional printing with echocardiographic data. Echo Res Pract 2016; 3: R57-R64
• 3 Bastarrachea RA, Chen J, Kent Jr JW. et al. Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design. IUBMB Life 2017; 69: 745-755
• 4 Krishna V, Sammartino F, Rezai A. A Review of the Current Therapies, Challenges, and Future Directions of Transcranial Focused Ultrasound Technology: Advances in Diagnosis and Treatment. JAMA Neurol 2017; DOI: 10.1001/jamaneurol.2017.3129.
• 5 Choi JJ, Feshitan JA, Baseri B. et al. Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo. IEEE Trans Biomed Eng 2010; 57: 145-154
• 6 Leinenga G, Götz J. Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med 2015; 7: 278ra3 doi:10.1126/scitranslmed.aaa2512
• 7 Walther A, Rippe L, Wang LV. et al. Analysis of the potential for non-invasive imaging of oxygenation at heart depth, using ultrasound optical tomography (UOT) or photo-acoustic tomography (PAT). Biomed Opt Express. 2017 8: 4523-4536
• 8 Votruba J, Zemanová P, Lambert L. et al. The Role of Airway and Endobronchial Ultrasound in Perioperative Medicine. Biomed Res Int 2015; DOI: 10.1155/2015/754626.
• 9 Darwiche K, Özkan F, Wolters C. et al. Endobronchial Ultrasound (EBUS) – Update 2017. Ultraschall Med 2018; 39: 14-38
• 10 Crisan M, Badea R, Crisan D. et al. Ultrasonography as a New, Non-Invasive Imagistic Technique Used for the Diagnosis and Monitoring of Psoriasis. In “An Interdisciplinary Approach to Psoriasis”. (InTech Open, 2017)
• 11 Dietrich CF, Bamber J, Berzigotti A. et al. EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017. Ultraschall Med 2017; 38: 377-394
• 12 van Sloun RJG, Wildeboer RR, Wijkstra H. et al. Viscoelasticity Mapping by Identification of Local Shear Wave Dynamics. IEEE Trans Ultrason Ferroelectr Freq Control 2017; 64: 1666-1673
• 13 Yilmaz R, Pilotto A, Roeben B. et al. Structural Ultrasound of the Medial Temporal Lobe in Alzheimer’s Disease. Ultraschall Med 2017; 38: 294-300
• 14 Jenssen C, Brkljacic B, Hocke M. et al. EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part VI – Ultrasound-Guided Vascular Interventions. Ultraschall Med 2016; 37: 473-476
• 15 Fusaroli P, Jenssen C, Hocke M. et al. EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V – EUS-Guided Therapeutic Interventions. Ultraschall Med 2016; 37: 412-420