A paper titled “The use of alendronate to enhance transcranial transmission of focused ultrasound for successful ablations in the brain” has been published in the high-ranking journal Ultrasonics  (Q1, IF 4.1). It was prepared by LIMU research fellows, Alisa Krokhmal and Vera Khokhlova, along with PhD student Daria Chupova, in collaboration with the V.S. Buzaev International Medical Center.

One of the key limitations for performing non-invasive thermal ablation of deep brain structures using Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is low ultrasound permeability of the skull. The main criterion for patient selection is the Skull Density Ratio (SDR). However, even with acceptable SDR values, the procedure can fail due to insufficient heating of the target area or severe pain caused by skull overheating.

The primary objective of the study was to evaluate the efficacy of alendronate (bisphosphonate) therapy for increasing the density and reducing the porosity of the skull trabecular bone tissue, thereby enhancing ultrasound permeability in patients with unsuccessful initial MRgFUS procedure.

The retrospective study included five patients with Parkinson’s disease, essential tremor, and dystonia with failed initial MRgFUS treatment. Over a period of 6–12 months, they received therapy with alendronic acid combined with vitamin D and calcium. Before and after the treatment, computed tomography (CT) scans of the head were performed to calculate SDR and construct histograms of bone density distribution (in Hounsfield units). A repeat MRgFUS procedure was then conducted along with evaluation of the achieved target temperature and the energy used for ultrasound emission.

Key results:

1. Following alendronate therapy, all repeat MRgFUS procedures were successful.
2. The average maximum focal temperature increased from 53.6 ± 4.0 °C to 55.7 ± 4.1 °C (p = 0.018).
3. SDR increased in 4 out of 5 patients.
4. Analysis of CT histograms showed reduced proportion of low-density voxels (i.e., decreased porosity) and densification primarily of the trabecular bone, resulting in a more homogeneous skull structure.
5. Visual analysis of registered CT images confirmed local bone densification in the most porous areas.

Thus, the study has shown that alendronate therapy may be an effective approach for improving skull ultrasound permeability and expanding the pool of patients eligible for MRgFUS treatment. Density histogram analysis provides valuable supplementary information to SDR for clinical decision-making.

For more details – see the text of the paper.