Biomedical Engineering Reference
In-Depth Information
showed a significant increase in the population of CD4 + lympho-
cytes (p < 0.01) and the ratio of CD4 + /CD8 + (p < 0.05) after HIFU
treatment. The abnormal levels of CD3 + lymphocytes returned to
normal in two patients, CD4 + /CD8 + ratio in three, CD19 + lym-
phocytes in one, and NK cell in one, respectively, in comparison
to the values in the control group. In addition, serum levels of
immunosuppressive cytokines including VEGF, TGF-β1, and
TGF-β2 were significantly decreased in peripheral blood of can-
cer patients after HIFU treatment, indicating that HIFU may
lessen tumor-induced immunosuppression and renew host anti-
tumor immunity [72].
Clinical evidence suggests that HIFU treatment may also
enhance local antitumor immunity in cancer patients. Kramer
and colleagues [73] found that HIFU treatment could alter the
presentation of tumor antigens in prostate cancer patients, which
was most likely to be stimulatory. Histological examination
showed significantly upregulated expression of HSP72, HSP73,
glucose regulated protein (GRP) 75, and GRP78 at the border
zone of HIFU treatment in prostate cancer. Heated prostatic can-
cer cells exhibited increased Th1-cytokine (IL-2, IFN-γ, TNF-α)
release but decreased Th2-cytokine (IL-4, -5, -10) release of TILs.
The upregulated expression of HSP70 was confirmed in the tumor
debris of breast cancer after HIFU ablation [74], indicating that
HIFU may modify tumor antigenicity to produce a host immune
response. Xu and colleagues [75] found the number of tumor-
infiltrating APCs, including DCs and macrophages, increased
significantly along the margin of HIFU-treated human breast
cancer, with an increased expression of HLA-DR, CD80, and
CD86 molecules. Activated APCs may take up HSP-tumor pep-
tide complex remaining in the tumor debris and present the chap-
eroned peptides directly to tumor-specific T lymphocytes with
high efficiency, resulting in potent cellular immune responses
against tumor cells after HIFU treatment. Furthermore, HIFU
could induce significant infiltration of TILs in human breast can-
cer, including CD3, CD4, CD8, B lymphocytes, and NK cells. The
numbers of the activated CTLs expressing FasL + , granzyme + , and
perforin + significantly increased in the HIFU-treated tumor, sug-
gesting that specific cellular antitumor immunity could be locally
triggered after HIFU treatment [76].
15.4.1 pre-HIFU planning
The process of HIFU treatment for the individual patient with
malignant tumor includes a number of steps, and each of these
steps requires special knowledge and close collaboration with
other members of the team to ensure accurate execution of a com-
plicated set of procedures. It begins with the pathologic diagnosis
of disease and accurate assessment of the tumor using TNM clas-
sification. As modalities for treating solid malignancy are usually
multiple, combining local therapies such as surgery or radiation
with systemic therapy such as chemotherapy, a decision as to
whether the planned treatment is curative or palliative is made
from a multidisciplinary clinical meeting held with surgeons,
oncologists, radiologists, radiation oncologists, and pathologists.
The role and scheduling of chemotherapy or vascular emboliza-
tion of the tumor in relation to a session of HIFU are defined
at the start. Subsequently, the location and extent of the tumor
relative to overlying and adjacent critical normal tissue are deter-
mined by a variety of imaging modalities. However, sometimes
pre-HIFU adjuvant treatments may influence the site and size of
the targeted volume. For instance, patients with typical osteosar-
coma are treated with several circles of neo-adjuvant chemother-
apy, and obvious regression of the tumor is usually observed in
these patients.
15.4.2 Imaging for HIFU planning
Imaging aspects includes tumor size, shape, number, margin,
and location within the organ relative to large blood vessel, ner-
vous fiber, and vital structures that might be at risk of injury
by the thermal ablation. Using contrast-enhanced technique,
tumor vascularity is assessed to determine the acoustic energy
distribution in the tumor.
Imaging taken for HIFU treatment planning is usually dif-
ferent from that taken for diagnostic use. Apart from imaging
aspects of the tumor, adjacent organs close to the targeted vol-
ume require attention for the purpose of safety. Using available
imaging techniques, the relationship between the tumor and its
surrounding organs is evaluated. For instance, a hepatic tumor
in the lower part of the left liver may be near to stomach, duo-
denum, and colon. Compared to magnetic resonance imaging
(MRI) and computed tomography (CT), real-time ultrasound
imaging is more important to assess the relationship between
the tumor and gastrointestinal tracts.
MRI and CT examinations include non-enhanced and con-
trast-enhanced scans. Either MRI or CT is selected to perform
for the acquisition of tumor data. The sequences used for imag-
ing are detailed in Section 15.6.
Ultrasound imaging includes B-mode imaging, color Doppler
and power ultrasound imaging, and contrast ultrasound exam-
ination. Attention must be given to the characteristics of the
tumor gray-scale, margin, motion, and vascularity, particularly
big blood vessels (more than 2 mm in diameter) in the tumor
and/or surrounding the tumor. If ultrasound imaging is used
for the guidance of ablative procedures, non-enhanced and
15.4 HIFU therapeutic plan
The aim of HIFU treatment is to deliver extracorporeal focused
ultrasound energy to a well-defined targeted volume at depth
through the intact skin, and thereby induce coagulation of the
tumor without causing damage to overlying or surrounding
vital structures. Because tumor geometry is usually complicated,
three-dimensional (3D) therapeutic planning based on images
is essential to achieve a complete ablation. The spatial distribu-
tion of thermal ablation delivered depends on a well-thought
out available plan, therapeutic device, and doctor expertise. The
processes of treatment planning for extracorporeal USgHIFU
system and technical considerations relative to this therapeutic
planning will be described in Section 15.4.6.
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