The goal of this clinical trial is to evaluate the safety and initial clinical effectiveness of MRI-guided focused ultrasound (MRgFUS) thermal ablation (capsulotomy) in patients with treatment-refractory anorexia nervosa (AN) and comorbid obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). The main questions it aims to answer are:

1. Can MR-guided focused ultrasound capsulotomy be safely delivered through an intact skull in patients with treatment-refractory anorexia nervosa and comorbid OCD and/or MDD, with a safety and side-effect profile comparable to traditional radiofrequency neurosurgical approaches?
2. Does MRgFUS capsulotomy produce clinical outcomes comparable to open surgical ablative procedures-specifically, improvements in anxiety, mood, quality of life, anorexia nervosa psychopathology, habit formation, and weight-in patients with treatment-refractory anorexia nervosa?

Participants will:

1. Undergo baseline imaging and clinical assessments
2. Receive a single MRgFUS capsulotomy targeting the ALIC
3. Be monitored for 24 months post-treatment to assess adverse events, quality of life, and symptom changes using standardized clinical and neuropsychiatric measures

This is a single-centre, prospective, single-arm, non-randomized Phase I study evaluating the safety, feasibility, and preliminary clinical benefit of MRI-guided focused ultrasound (MRgFUS) for the treatment of treatment-refractory anorexia nervosa (AN) with comorbid obsessive-compulsive disorder (OCD) and/or major depressive disorder (MDD).

A total of 10 patients will be enrolled and treated with a single MRgFUS capsulotomy targeting the anterior limb of the internal capsule (ALIC).

Participants will undergo comprehensive pre-treatment evaluations, including psychiatric assessment, physical and nutritional status review, MRI imaging, and surgical eligibility screening. The treatment will be performed using the ExAblate 4000 system under continuous MRI guidance and real-time thermometry.

Participants will be followed at regular intervals, including immediately post-treatment and at 1, 3, 6, 12, 18, and 24 months post-procedure, to evaluate safety and changes in clinical symptoms.

Inclusion Criteria:

1. Men and women ≥18 and ≤65 years of age, inclusive.

2. Patients who are competent and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.

3. DSM-V diagnosis of Anorexia Nervosa, with co-morbid diagnosis of OCD and/or Major depressive disorder.

4. Treatment refractoriness indicated by any of:

   1. Duration of illness more than 10 years with no more than three months of remission in terms of weight;
   2. At least three attempts at expert hospital based treatment that were not successful or where there was no sustained response to treatment;
   3. A pattern of increased medical instability requiring at least two episodes of emergency/involuntary re-feeding and lasting at least two years;

5. Ability to provide informed consent/competent to make medical decisions.

Exclusion Criteria:

1. Patients with unstable cardiac status [e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP > 100 on medication)]
2. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
3. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal INR)
4. Cerebrovascular disease (e.g. CVA within 6 months) or history of intracranial hemorrhage
5. Untreated, uncontrolled sleep apnea
6. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure
7. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment
8. Are participating or have participated in another clinical trial in the last 30 days
9. Patients unable to communicate with the investigator and staff.
10. Presence of significant cognitive impairment
11. History of psychosis on clinical evaluation.
12. Patients with brain tumors already known or revealed on pretreatment MRI
13. Currently pregnant (as determined by history and serum HCG) or lactating.
14. Chemical abuse or dependence within the previous six months
15. Presence of a metabolic pathology interfering with eating or digestion (e.g. diabetes).
16. Body mass index (BMI) less than 13