Proposed US/MRI registration approach

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External Beam Radiation Therapy (EBRT):

EBRT is a type of radiation therapy that consists in destroying the cancerous cells by irradiating the prostate with an external source of ionizing radiation. X-rays are produced by a linear accelerator (linac) (see figure 1.5). Linac transmits photon beams in different angles in order to irradiate the whole volume of the structure of interest. These angles are determined using radiological images where the tumor’s location is mapped out at first, and then X-ray beams are delivered to that location. The treatment planning is highly dependent on the placement of the patient. Linac rotates around a point, called isocenter, which is situated at 100 cm from the source of the radiation and should be placed in the center of the target volume. In order to correctly place the isocenter, the treatment planning system determines how the patient should be placed on the table. The radiotherapist prescribes the dose that should be applied on the tumor. Afterwards, and using the treatment planning system, the dose distribution is calculated using Computed Tomography (CT) images, as shown in figure 1.6.
For PCa, EBRT is usually performed in the cases of a localized cancer as well as when the tumor is locally advanced. It can also be applied after prostatectomy if a biopsy indicated that the tumor has not been removed during the surgery. The main drawback of EBRT is that the X-ray beams, when pointed at the organ of interest, are delivered to that organ as well as the areas around it. Side effects are usually limited to the part of the patient’s body that received the radiation. They include however urinary incontinence and erectile dysfunction.

Brachytherapy:

Brachytherapy, also known as internal radiotherapy, is a type of radiation therapy where the irradiation is delivered by inserting radioactive sources inside the structure of interest, temporarily or permanently. In the case of PCa, radioactive sources are inserted via needles that go through the perineum. Brachytherapy has the advantage of delivering a high dose of irradiation to the prostate while sparing the surrounding healthy tissues; namely the rectum and bladder. According to [2, 15], brachytherapy has several advantages and better quality-of-life when compared to other treatment techniques:
– It is minimally invasive
– It requires a short hospital stay
– Patient exposure to ionizing radiation is minimized, compared to EBRT.
– Lower cost.
In the United States, 60000 patients underwent brachytherapy in 2006, which represents 35% of the treatment techniques. In other countries such as Germany, Netherlands, England and Spain, brachytherapy represents between 5 and 12 % only. In France, despite the very encouraging results of this treatment, the ratio is still as low as 3%. This is due to the late and insufficient valorization that does not reflect the actual costs of the medical work and the necessary environment. Major urological French and European societies consider brachytherapy as a standard treatment for PCa, they also encourage exploiting this technique since it has several advantages when compared to other techniques [2]. The number of treatments with this technique is however increasing from one year to another; from 1636 in 2007 it has reached 4000 treatments in 2015.
Unlike other techniques, brachytherapy has been practiced for almost two decades in France. The feedback from the research and practice that has been done on brachytherapy gave very good long-term results and a better quality-of-life for patients undergoing this treatment when compared to other treatment techniques; making brachytherapy the current technique of choice when treating early-stage prostate cancers. In addition, brachytherapy also allows focal treatments, which are characterized by having minimum side effects.

Hormone therapy:

Hormone therapy, also called Androgen Deprivation Therapy (ADT), consists in reducing the levels of male hormones (androgens) which stimulate prostate cancer cells to grow. Testosterone is the main androgen responsible for prostate cancer cells growth. Therefore, ADT involves blocking the testosterone from being released into the prostate. This may make the prostate shrink or grow more slowly but generally, when applied alone, it does not cure prostate cancer. This kind of treatment is delivered mainly to older men, men diagnosed with a cancer where lymph nodes are involved or a cancer accompanied by extensive metastases.
Although most of prostate cells respond to the removal of this hormone, some cells grow independently of androgens, and therefore are not affected by this kind of therapy. Side effects of hormone therapy include erectile dysfunction, loss of bone density, low red blood cell counts, loss of muscle mass and physical strength.

Chemotherapy:

Chemotherapy is a type of therapy that makes use of chemicals, or anti-cancer drugs, to destroy the cancerous cells. It is generally used in certain cases where the cancer is hormone-resistant. The efficacy of chemotherapy depends on the type and stage of the cancer. It is usually used to relieve symptoms associated with metastatic disease. However, this treatment is sometimes completely ineffective in cases such as brain tumors. The main inconvenience of this kind of treatment is that it has, as any other drug, several side effects on the body including hair loss, nausea, vomiting, diarrhea, fatigue (low red blood cell counts) and increased chance of infections (low white blood cell counts).

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High-Intensity Focused Ultrasound (HIFU):

HIFU can also be considered when the radiation treatments fail in the case of a low risk cancer or a localized PCa. It consists in destroying cancerous cells by heating the prostate. TRUS is used to transmit ultrasonic beams, in duration of five seconds, to a target localized zones of the prostate. HIFU has the advantage of being radiation-free and therefore no irradiation-related side effects are caused by such a treatment. It is also non-invasive, so no incisions are made like in the case of a prostatectomy. HIFU is performed in only 180 centers around the world, 38 of which are in France. The French Association of Urology (L’association française d’urology) recommends HIFU when the patient is over 70 years old and when the prostate volume is less than 40 cm3 [16]. According to [16], patients who underwent HIFU have less urinary incontinence when compared to other treatments. However, some medical associations do not recommend HIFU because they think that more research should be done including clinical trials evaluating the quality-of-life and the long-term survival of patients undergoing this kind of treatment [17].

Cryotherapy:

Similarly to HIFU, cryotherapy is another focal treatment that can also be considered when the radiation treatments fail in the case of a low risk or localized PCa. This treatment consists in decreasing the growth and reproduction of cancerous cells by freezing the prostate tissues. It is used to treat localized cancers while sparing other prostate tissues, but also low volume cancers. Its main objective is to provide adequate cancer control while minimizing the side effects [18]. However, this technique is still under evaluation for the treatment of PCa.

Other focal therapies:

While cryotherapy and HIFU are currently the two modalities with the most long-standing experience in focal therapy, other Focal Laser Ablation (FLA) techniques are currently under investigation; such as Photodynamic Therapy (PDT) and Laser Interstitial Thermo Therapy (LTIT). FLA is an intermediate option between active surveillance and radical prostatectomy for small and low risk PCa. In such laser-based procedures, laser energy is used to ablate only the index lesion while minimizing the damage to the surrounding structures [19]. Light energy is delivered to target cancerous cells via a fiber-optic catheter. Subsequently, computer-guided laser ablation is performed under real-time MRI guidance. FLA techniques have fewer side effects than other treatments, and they are minimally invasive procedures [20]. However, these techniques are still under evaluation and need more clinical trials to study their safety and effectiveness.
In this work, we will focus on brachytherapy considering that it has been practiced and investigated since the 90’s with good long-term results showing several advantages; better quality-of-life and fewer side effects when compared to other treatment techniques [2, 15]. Hereafter, the clinical context of brachytherapy is explained in details. The problems and the challenges in this kind of treatment are highlighted, leading to the proposed approach that overcomes these problems.

Table of contents :

1. Introduction
1.1 Prostate Cancer
1.1.1 Prostate
1.1.2 Risk factors
1.1.3 Diagnosis
1.1.4 Treatment
1.2 Brachytherapy
1.2.1 Clinical context
1.3 Objectives of the thesis: Image-guided brachytherapy
1.4 Conclusion
2. Pre-operative MRI/CT Registration
2.1 Principles of image registration
2.1.1 Classification of registration methods
2.1.2 Components of registration
2.2 State of the art of MRI/CT registration
2.3 Proposed MRI/CT registration approach
2.3.1 VOIs determination
2.3.2 Registration
2.4 Implementation
2.5 Conclusion
References
3. Intra-operative US/MRI Registration
3.1 State of the art of US/MRI registration
3.1.1 Surface-based registration methods
3.1.2 Point-based registration methods
3.1.3 Intensity-based registration methods
3.2 Proposed US/MRI registration approach
3.2.1 Optional preprocessing
3.2.2 VOIs determination
3.2.3 Registration
3.3 Implementation
3.3.1 GPUs
3.3.2 GPU implementation
3.4 Conclusion
References
4. Evaluation and Results
4.1 Prostate phantom
4.1.1 MRI phantom
4.1.2 US phantom
4.2 Clinical patient datasets
4.2.1 Pre-operative MRI/CT registration
4.2.2 Intra-operative US/MRI registration
4.3 Evaluation metrics
4.3.1 Visual assessment
4.3.2 Quantitative criteria
4.3.3 Reproducibility and robustness
4.4 Results
4.4.1 Pre-operative MRI/CT registration
4.4.1.1 Setting the parameters of the optimizer
4.4.1.2 Evaluation metrics
4.4.2 Intra-operative US/MRI registration
4.4.2.1 Prostate phantom
4.4.2.2 Clinical patient datasets
A. Mutual Information
B. LC2
C. Evaluation metrics
4.4.3 Final US/CT registration
4.5 Conclusion
5. Discussion and Conclusion
5.1 Pre-operative phase
5.2 Intra-operative phase
5.3 Conclusion and future work
References

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