Applications of Focused Ultrasound in Cerebrovascular Diseases and Brain Tumors

Abstract

Oncology and cerebrovascular disease constitute two of the most common diseases afflicting the central nervous system. Standard of treatment of these pathologies is based on multidisciplinary approaches encompassing combination of interventional procedures such as open and endovascular surgeries, drugs (chemotherapies, anti-coagulants, anti-platelet therapies, thrombolytics), and radiation therapies. In this context, therapeutic ultrasound could represent a novel diagnostic/therapeutic in the armamentarium of the surgeon to treat these diseases. Ultrasound relies on mechanical energy to induce numerous physical and biological effects. The application of this technology in neurology has been limited due to the challenges with penetrating the skull, thus limiting a prompt translation as has been seen in treating pathologies in other organs, such as breast and abdomen. Thanks to pivotal adjuncts such as multiconvergent transducers, magnetic resonance imaging (MRI) guidance, MRI thermometry, implantable transducers, and acoustic windows, focused ultrasound (FUS) is ready for prime-time applications in oncology and cerebrovascular neurology. In this review, we analyze the evolution of FUS from the beginning in 1950s to current state-of-the-art. We provide an overall picture of actual and future applications of FUS in oncology and cerebrovascular neurology reporting for each application the principal existing evidences.

Keywords: Neuro-oncology; cerebrovascular neurology; focused ultrasound; neurosurgery; therapeutic ultrasound.

Fig. 1

Thermal ablation. Schematic representation of thermal ablation mechanism and specificity.

Fig. 2

Kranion software. Different screenshots of Kranion, a modeling software for transcranial focused ultrasound treatment. (A) Pretreatment CT and MRI scan are fused and used to plan treatment taking into account bone density and structure in order to set the phases of each single transducer insonation. Red dots represent not usable transducers while the green dots refer to the potentially employable. (B, C) Green, yellow, and red areas represent the treatment envelope or the volume in which the maximal energy could be deployed. (D) Each transducer insonation path is displayed converging to the target. (E, F) MRI thermometry allows to plan and monitor FUS treatment; note the specificity of thermal generation in the left panel (in red maximal and in green average temperature are displayed).

Fig. 3

Mechanical destruction. Schematic representation of mechanical destruction mechanism and specificity.

Fig. 4

BBB disruption. Schematic representation of BBB opening mechanism.

Fig. 5

Sonoporation. Schematic representation of sonoporation mechanism and specificity.

Fig. 6

Immunomodulation. Schematic representation of the different mechanisms behind FUS immunomodulation.

Fig. 7

Sensitization to radiotherapy. Schematic representation of the potential role of FUS in reducing radiotherapy exposure.

Fig. 8

Sonodynamic therapy. Schematic representation of sonodynamic therapy mechanism and specificity.

Fig. 9

Clot lysis. Schematic representation of clot lysis mechanism.

Fig. 10

MB distribution. Intra-operative navigated contrast-enhanced ultrasound in a case of right parasagittal meningioma in the venous phase. MBs are mainly confined in posterior venous circulation. Note the different enhancement of brain parenchyma and corpus callosum (T = tumor, cc = corpus callosum, icv = internal cerebral veins, iss = inferior sagittal sinus, g = galen vein).