Biomedical Engineering Reference
In-Depth Information
were generally conducted by “external counting” or “scintillation scanning.” for that,
a handheld geiger-Muller counter introduced in 1928 capable of measuring gamma-
rays and its mica-window modification for simultaneous detection of energetic beta-
rays from in vivo sources was utilized [11]. By applying a geiger-Muller counter to
the surface of the skin at the site of interest, the distribution of the isotopes in the blood
and extracellular tissue fluids could be followed. This method was a widely accepted
standard in clinics until in 1958 when H. anger from Berkeley lab described a new
scintillation camera (anger camera), where gamma-rays were detected by a scintil-
lating crystal. Upon contact with a gamma photon, a scintillator such as NaI crystal
emits a photon at much lower energy, approximately 430 nm, thus converting ionizing
radiation into light energy that could be detected by a photomultiplier tube (PMT).
With many of the PMT tubes attached to the same crystal, many points could be imaged
simultaneously. One of the first applications of the anger camera was in a knee injected
with 198 au to diagnose an acute knee diffusion [12], a pathology that describes an
excessive amount of fluid that accumulates around the joint and causes swelling.
Positron emission tomography (PeT) and single-photon emission computed
tomography (SPecT) have made their appearance in the 1950s. at the beginning of
this decade, a team from MIT led by g. Brownell and physician W. Sweet from
Massachusetts general Hospital [13] and independently f. Wrenn et al . [14] con-
structed the first PeT detector to exploit the positron-electron annihilation effect for
use as an imaging tool. D. Kuhl at the University of Pennsylvania and his colleagues
at the University of Pennsylvania built the Mark II scanner, an ancestor of today's cT
and SPecT scanners. The historical reviews on the development of imaging tech-
niques written by the pioneers of this field describe these early efforts in great detail
[15-17]. One of the first human scanners Mark III is shown in figure 1.4.
although the period of the 1940s-1950s has demonstrated the potential of imaging
with nanoparticles in diagnostics and treatment monitoring, the use of nanoparticles
was accidental. The majority of the efforts were directed toward the discovery of less
expensive and more available sources of radioisotopes (cyclotrons, nuclear reactors),
the development of imaging instrumentation, and the medical assessment of the tech-
niques. Nanoparticles were produced mostly in the form of colloids, their chemistry
has more or less been established, and their formulations were straightforward.
Minimum efforts have been made to modify the nanoparticles for specific medical
applications. These efforts started and went into full swing throughout the next decades.
1.4
imaging witH liPosomes (1960s-1970s)
1.4.1
discovery of liposomes
In the beginning of the 1960s, a. Bangham and his colleagues from the University of
cambridge (london) visualized the dispersion of lecithin-type phospholipids under
an electron microscope and discovered their unusual multilamellar architecture
(fig. 1.5). “Toward the end of 1962, we had persuaded ourselves that we were seeing
minute sacs of approximately 50 nm diameter, the first 'lipid somes' as we have come
to know them.” Intensive studies of the liposomes led to the discovery of aqueous
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