Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1998-03-13
2001-02-06
Casler, Brian L. (Department: 1911)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
C600S420000, C324S309000
Reexamination Certificate
active
06185444
ABSTRACT:
BACKGROUND OF THE INVENTION
The bones of a skeletal system have a dense outer shell, or cortex, made of cortical bone (alternatively termed “compact” or “dense” bone). Inside the cortex, many types or regions of bone also have a mesh or network of trabecular bone (alternatively termed “spongy” or “cancellous” bone), made up of roughly the same material as the cortical bone. The region or regions enclosed by the cortex and/or the trabecular network contain marrow, and are aptly termed the “marrow space.” In other types or regions of bone, particularly long bones such as femurs, the cortical bone encloses a trabecular-free marrow space, termed the “medulla” or the “medullary cavity.” Regardless of whether it is contained in the trabecular network or the medullary cavity, marrow is comprised of living matter, including cells and a circulatory system, that supports the living constituents of the bone. Marrow also contains fat, and houses certain components of the blood-forming and immune systems of the body.
The dense bone material that makes up the cortical and trabecular bone is a composite material, made up of organic and inorganic constituents, intimately mixed. The organic constituents are alternately termed the “matrix” or “osteoid,” and are comprised primarily of the protein collagen. The matrix is cartilage-like and flexible, and gives the bone material elasticity arid toughness.
The inorganic constituents are extremely small mineral crystals, carried and bound into a cohesive mass by the matrix, and give the bone its hardness and compressive strength. The crystals are typically flat plates on the order of hundreds of Angstroms or less on a side, and tens of Angstroms in thickness. The mineral crystals comprise about 60 to 70 percent of the total dry weight of dense bone.
A healthy human skeletal system among other things structurally supports the body, provides a set of levers for the mechanical actions of the skeletal muscles, protects the internal organs, houses parts of the blood-forming and immune systems, and functions as a storage reservoir for phosphate, calcium and other ions.
In an unhealthy skeletal system, one or more of these features may be compromised or lost. In the bone disease osteoporosis, the amount of bone in the skeleton is reduced, leading to weak and brittle bones and an increased risk of fracture. In Paget's disease, the rate at which bone mineral and matrix are cyclically resorbed (dissolved) and deposited is abnormally high, leading to distorted bone structure and pain. In osteomalacia (which is known as rickets when it affects growing children), there is an insufficient proportion of mineral to matrix. And in some instances, a bone fracture will not heal because of a failure in the bone reconstruction mechanism, a pathological condition known as nonunion.
SUMMARY OF THE INVENTION
In one aspect of the invention, an object comprising an isotope is subjected to a main magnetic field, as well as to a pulse sequence in which an RF excitation pulse is generated during a magnetic field gradient pulse. RF signals emitted by the excited isotope are acquired after the RF pulse, and then processed to generate data representative of the spatial distribution of the isotope within the object.
Because the magnetic field gradient pulse is initiated prior to the RF excitation pulse, the acquisition of the emitted RF signals can begin almost immediately following the conclusion of the RF excitation pulse. There is no need to wait for the gradient pulse to ramp up and stabilize, and/or for eddy currents to decay, after the RF pulse. This reduces the “deadtime” (the time during which the, e.g., analog-to-digital converter is unable to sample emitted RF signals) between the end of the RF pulse and the start of sampling. Reducing deadtime is an important consideration when imaging an isotope with a relatively short transverse relaxation time T
2
, such as an isotope carried in solid-state in the object being imaged. If the gradient pulse were generated after the RF pulse, the MR signal from such solid-state isotopes might largely or entirely disappear by the time the gradient ramped up and stabilized. Initiating the gradient pulse prior to the RF excitation pulse further allows the gradient rise time to be relatively long (i.e., the rate of change of magnetic flux (dB/dt) to be relatively low), and thus guards against causing nerve stimulation in the subject being imaged. For example, the rise time can be on the order of 0.1 s, even when the T
2
for the isotope of interest (e.g., solid-state phosphorus-31 (
31
P) in bone) is on the order of 100 &mgr;s.
Embodiments of this aspect of the invention include the following features. Two additional gradient pulses are generated, such that the three gradient pulses are mutually orthogonal, and define a gradient vector. All three gradient pulses are initiated prior to the RF excitation pulse, and the RF pulse is generated during the three gradient pulses (e.g., 200 &mgr;s after the gradient pulses rise to full amplitude). The acquisition of RF signals emitted by the excited isotope occurs during the generation of the three gradient pulses, and begins substantially immediately (e.g., less than 40 &mgr;s, preferably less than 20 &mgr;s, and more preferably less than 5 &mgr;s) after the conclusion of the RF excitation pulse.
The pulse sequence comprising the three orthogonal gradient pulses and the RF excitation pulse is executed a plurality of times, e.g., on the order of one thousand times. Each pulse sequence has an associated gradient vector. Although these vectors all have substantially the same magnitude, e.g., a value between 2 and 12 G/cm such as 9 G/cm, each vector has a unique direction.
Repeating this set of sequences permits signal averaging to increase the signal-to-noise ratio (SNR). If the entire set of about one thousand gradient vectors is repeated four times (i.e., if each vector is generated on four separate occasions), then there are about four thousand total acquisitions. The acquisitions can occur in any order.
To keep the total sampling time relatively short, the interpulse repetition time TR is less than about 1.0 s, more preferably less than about 0.5 s, and even more preferably less than about 0.3 s. The flip angle of the RF excitation pulse is less than about 30°, more preferably less than about 20°. Although this results in sampling only a portion of the longitudinal magnetization M, it permits shorter interpulse repetition times TR and improves signal-to-noise ratio for a fixed image scan time.
The acquired RF signals emitted by the excited isotope reside on radial lines in a spherical polar coordinate system in the k-space (the Fourier transform of the image), wherein the points in the spherical polar coordinate system can be represented by vectors k from the origin. In processing these data, each is multiplied by its associated ¦k¦
2
(the square of the magnitude of k), and then interpolated onto a three-dimensional Cartesian grid before being subjected to Fourier transformation.
Processing the acquired RF signals further includes generating data representative of the density of the isotope, e.g.,
31
P or
1
H, in the object, e.g., a region or specimen of bone. In determining the spatial density of
31
P in a specimen of bone, a calibration phantom comprising a known density or densities of
31
P can be positioned near the bone and subjected to the main magnetic field and pulse sequence, such that the acquired RF signals can be processed to yield an image of both the bone specimen and the phantom. The
31
P density in the bone specimen can be assessed by comparing the intensity of the specimen image to the intensity of the phantom image.
In still other embodiments, RF excitation pulses can excite plural isotopes, e.g.,
31
P and/or
1
H, and RF signals emitted by both isotopes can be acquired and processed to generate data representative of the spatial distribution of either or both of the two isotopes within the object, e.g., spatial density data. The data sets can be compared and contrast
Ackerman Jerome L.
Glimcher Melvin J.
Wu Yaotang
Casler Brian L.
Fish & Richardson P.C.
SkelScan, Inc.
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