U.S. patent application number 14/806472 was filed with the patent office on 2016-01-21 for method for thoracic vertebral bone density measurement by thoracic quantitative computed tomography.
This patent application is currently assigned to Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center. The applicant listed for this patent is Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center. Invention is credited to Matthew J. Budoff, Christopher A. Dailing, Song Shou Mao.
Application Number | 20160015346 14/806472 |
Document ID | / |
Family ID | 44505648 |
Filed Date | 2016-01-21 |
United States Patent
Application |
20160015346 |
Kind Code |
A1 |
Budoff; Matthew J. ; et
al. |
January 21, 2016 |
METHOD FOR THORACIC VERTEBRAL BONE DENSITY MEASUREMENT BY THORACIC
QUANTITATIVE COMPUTED TOMOGRAPHY
Abstract
A technique for measuring thoracic vertebral bone density (BMD)
and coronary calcium score (CCS). Representatively, BMD was
measured and averaged at three consecutive thoracic spines (3T)
starting from the left main coronary artery caudally and averaging
the results of the measurements at the first, second and third
spine regions to obtain a thoracic trabecular bone mineral density
measurement. The "reference", as the 3T BMD value of 30 year old
and the piBMD (predicted individual BMD (piBMD) were developed.
Based on the "reference", and piBMD, T and Z score of 3T formula
were derived in both genders. The new calibration phantom of TQCT
and LQCT was designed. The ratios of CTHU/mg/cc were obtained with
varying scanners, which were used to translate the CTHU to density
units (mg/cc) in BMD and CCS mass measurement. A processor capable
of quantitating both BMD and CCS burden was designed. In image
without a calibration phantom, formulas were created to quantitate
BMD with a high precision.
Inventors: |
Budoff; Matthew J.;
(Manhattan Beach, CA) ; Mao; Song Shou; (Lakewood,
CA) ; Dailing; Christopher A.; (Long Beach,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Los Angeles BioMedical Research Institute at Harbor-UCLA Medical
Center |
Torrance |
CA |
US |
|
|
Assignee: |
Los Angeles BioMedical Research
Institute at Harbor-UCLA Medical Center
|
Family ID: |
44505648 |
Appl. No.: |
14/806472 |
Filed: |
July 22, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13031047 |
Feb 18, 2011 |
9119590 |
|
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14806472 |
|
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61305698 |
Feb 18, 2010 |
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Current U.S.
Class: |
378/4 ;
702/19 |
Current CPC
Class: |
G01N 23/046 20130101;
A61B 5/4566 20130101; A61B 6/032 20130101; A61B 6/5294 20130101;
A61B 6/504 20130101; G06K 9/52 20130101; G06K 2209/05 20130101;
A61B 6/505 20130101; A61B 6/4435 20130101; A61B 6/5217 20130101;
G06K 2009/4666 20130101; A61B 6/0407 20130101; G06K 9/6267
20130101; A61B 5/4509 20130101; A61B 6/5205 20130101 |
International
Class: |
A61B 6/00 20060101
A61B006/00; A61B 6/03 20060101 A61B006/03 |
Claims
1. A method comprising: obtaining an image of a spine region at a
level comprising a left main coronary artery; identifying a portion
of the image comprising a body location level comprising the left
main coronary artery; identifying a cerebral center at a spine
region containing the left main coronary artery; measuring a bone
mineral density at a first spine region containing the left main
coronary artery; measuring a bone mineral density at a second spine
region following the spine region containing the left main coronary
artery; measuring a bone mineral density at a third spine region
following the second spine region containing the left main coronary
artery; and averaging the results of the measurements at the first,
second and third spine regions to obtain a thoracic trabecular bone
mineral density measurement.
2. The method of claim 1, wherein the image is a computed
tomography (CT) image containing a heart and a thoracic spine.
3. The method of claim 1, wherein the image is a computed
tomography (CT) image containing the left main coronary artery and
at least three thoracic spines.
4. The method of claim 1, wherein the image is a computed
tomography (CT) image obtained at a temporal resolution of less
than 400 milliseconds/rotation.
5. A system comprising: a computing device for averaging the
results of a measurement of bone mineral density at a first spine
region, a second spine region and a third spine region to obtain a
(3T) thoracic trabecular bone mineral density measurement.
6. A machine readable medium containing a set of instructions that
when executed cause a computing device to perform a method
comprising: averaging the results of a measurement of bone mineral
density at a first spine region, a second spine region and a third
spine region to obtain a thoracic trabecular bone mineral density
measurement.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation application of U.S.
patent application Ser. No. 13/031,047, filed Feb. 18, 2011, and
entitled "METHOD FOR THORACIC VERTEBRAL BONE DENSITY MEASUREMENT BY
THORACIC QUANTITATIVE COMPUTED TOMOGRAPHY", which claims the
priority benefit of U.S. Provisional Patent Application Ser. No.
61/305,698, filed Feb. 18, 2010, and entitled "METHOD FOR THORACIC
VERTEBRAL BONE DENSITY MEASUREMENT BY THORACIC QUANTITATIVE
COMPUTED TOMOGRAPHY", both of which being incorporated herein by
reference in their entirety.
FIELD
[0002] A method for measurement of thoracic vertebral bone
density.
BACKGROUND
[0003] Osteoporosis is the most common metabolic disorder of bone.
The World Health Organization (WHO) estimates that 70 million
people worldwide have osteoporosis. The annual worldwide incidence
of hip fracture is 1.5 million, a number projected to grow to 2.6
million by 2025 and to 4.5 million by 2050. Bone strength is mostly
dependent on its mineral content and therefore the measurement of
bone mineral content is important to predict osteoporosis-related
fractures. The most frequent site involved in fractures is the
thoraco-lumbar junction, with mid-thoracic spine being the second
most common site. The spine is the most sensitive site and is
usually the first site to experience osteoporosis fractures. The
bone turnover rate of the spinal trabecular bone is significantly
higher than the cortical bone (the spinal trabecular bone
remodeling rate is 5-10 times higher than the cortical bone).
[0004] Quantitative computed tomography (QCT) is a technique for
three-dimensional bone mineral density (BMD) measurement. The bone
density can be measured separately in the trabecular and cortical
bone compartments. Therefore, thoracic quantitative computed
tomography (TQCT) is an important technique for estimating and
monitoring bone strength, especially in thoracic BMD
measurement.
[0005] Cardiovascular diseases in general and coronary artery
disease in particular remain the number one cause of death and
disability in all industrialized and in many developing countries
all over the world. In 2002, coronary artery disease, also referred
to as coronary heart disease (CHD), caused 7.2 million deaths
worldwide. Each year there are about 5.8 million new CHD cases, and
about 40 million individuals with preventable CHD are alive today.
The presence of calcium deposits in the coronary arteries has been
well recognized as a marker of atherosclerotic coronary artery
disease and gives independent incremental information, in addition
to the traditional risk factors, in predicting cardiac events.
Electron beam computed tomography (EBCT) has successfully been used
to quantify plaque burden (by scoring calcification in the coronary
arteries) over the past 20 years. Currently the cardiovascular CT
scan is used widely to estimate calcium score and these scanners
have obtained significantly higher temporal, special and contrast
resolution with a significant decrease in radiation dosage using
prospective triggering techniques. Current calcium scoring systems
have a step-wise increase in scores that leads to decreased
reproducibility using the Agatston score method. The most common
current scoring system is one that uses the peak CT density, with a
score of 1 applied for HU of 130-199, 2 for 200-299, 3 for 300-399
and 4 for 400 and greater. This impairs rescan reproducibility.
[0006] There is a significant positive association between BMD
values obtained from the thoracic and lumbar spinal vertebrae
(r=0.93 in female and r=0.88 in male). Even the cervical spine BMD
is also reported to be significantly correlated with the lumbar BMD
(r=0.66 to 0.87). In this aspect, it has been shown that the TQCT
with CAC scans give an adequate measure of BMD with a high degree
of precision and reproducibility. Therefore, the thoracic cardiac
scan is likely to be a useful ancillary assessment of bone mineral
status in the population in general.
[0007] However, a significant difference in the BMD measurements
found using the TQCT technique and the lumbar quantitative computed
tomography (LQCT) technique has been reported (i.e., a different of
5.8-13.9%) and our study result (9.6% in female and 10.4% in male).
This variation can be caused by various factors: such as scanner
type, scan protocol, scan technique parameter, patient's age
contribution, patient's status, etc. Bone density and loss rate
have significant differences between lumbar and thoracic spines,
therefore one cannot use current LQCT standard in TQCT measurement
directly. The validating study is necessary to develop a method and
reference standard by TQCT scan.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The following illustration is by way of example and not by
way of limitation in the figures of the accompanying drawings in
which like references indicate like elements. It should be noted
that references to "an" or "one" embodiment in this disclosure are
not necessarily to the same embodiment, and such references mean at
least one.
[0009] FIG. 1 illustrates a computed tomography scanner (CT)
system.
[0010] FIG. 2 is a flowchart illustrating one embodiment of a
method for determining thoracic bone mineral density.
[0011] FIG. 3 is a flowchart illustrating one embodiment of a
method for determining thoracic bone mineral density.
[0012] FIG. 4 illustrates an image displayed by a computing device
of TQCT and LQCT.
[0013] FIG. 5 illustrates one embodiment of calibration phantom
used to translate CTHU to BMD (mg/cc), to calculate CAC mass score
and calibrate CAC score.
[0014] FIG. 6A illustrates the profile of BMD in female
population.
[0015] FIG. 6B illustrates the profile of BMD in male
population.
DETAILED DESCRIPTION
[0016] A technique for determining bone mineral density (BMD) by
using thoracic quantitative computed tomography (TQCT) with
coronary artery calcium (CAC) scan is disclosed herein. As
previously discussed, there are significant variations in lumbar
and thoracic BMD of the same object due to the variation in scanner
and scan protocol. The description provided herein discloses a
technique for obtaining consistent BMD measurements regardless of
the scanner used. The technique generally includes the use of a CT
scanner to obtain a heart image of a desired coronary calcium scan.
Data from the CT scanner is reconstructed into an image by a
computing device. Beginning at the left main coronary artery level,
the bone mineral density of three consecutive thoracic regions (3T)
is measured and averaged to obtain thoracic bone mineral density. A
T score measured by the TQCT can be used to estimate osteoporosis
in the general population. A comparable T score with lumbar
quantitative computed tomography (LQCT) in a subject who had a
previous LQCT scan can be determined using the formulas disclosed
herein. Similar T scores between TQCT and LQCT can be obtained
using the formulas disclosed herein.
[0017] As previously discussed, current calcium scoring systems
have a step-wise increase in scores that leads to decreased
reproducibility using the Agatston score method. The most common
current scoring system is one that uses the peak CT density, with a
score of 1 applied for HU of 130-199, 2 for 200-299, 3 for 300-399
and 4 for 400 and greater. This impairs rescan reproducibility. For
those reasons, the new scoring method disclosed herein uses the
mean (not peak CTHU) CTHU/100 as the calcium lesion density scale.
In particular, the score=area (mm2).times.mean CTHU/100. At the
time of coronary artery calcium (CAC) scan, the BMD of mid to lower
thoracic spine can be measured simultaneously by using the TQCT
technique.
[0018] A formula to translate the CTHU to mg/cm.sup.3 may be
generated and also used in CT CAC scan without calibration
phantoms.
[0019] The CAC scan (row data) is completed with cardiovascular CT
(electron beam CT-EBT or multiple detector row CT-MDCT) by using a
snap shot protocol. By using this row data, a reconstructed image
is completed with a field of view size (FOV) in 35-40 cm. In these
images, the heart and 3-4 entire thoracic spine regions are
included on mid to end thoracic segments. A computing device is
used to measure the score of calcium burden and to estimate the
risk possibility of coronary artery disease in the studied subject
based on the images. A computing device may further be used to
measure BMD from the images. The thoracic spine number and starting
level covered by these CAC scans varies. The site of origin of left
main (LM) coronary artery in all scans was at the level of T7, T8,
T6 and T9 in about 50%, 30%, 19% and 1% cases respectively
(computed from 300 cases with whole body scan). Three thoracic BMD
measurements are made by the computing device starting at the level
containing the left main (LM) coronary artery. The frequency
consists of three thoracic series in 50%, 30%, 19% and 1% in four
groups (6-8, 7-9, 8-10 and 9-11) respectively. The variation of
measured BMD values within the 4 groups is about 1-2%.
[0020] The measurement of the thoracic vertebrae BMD was started at
the slice level containing the left main coronary artery in all the
CAC scans. The thickness of the region of interest (ROI) was 10 mm
by Q5000 and 6 mm by NVivo. The center of ROI was located at the
center of the vertebrae at a distance of 2-3 mm from the spinal
cortical bone. The cortical bone, area with large venous vessel,
islanded bone and calcifying herniated disk were excluded as much
as possible from the ROI by using the free tracing protocol.
[0021] The mean BMD value of the three thoracic spines (3T) was
calculated in all measurements. The 30 subgroups were formed based
on two aging intervals in each gender (Table I).
[0022] The formula to calculate a predicted individual BMD (piBMD)
in both genders was generated using the 30 subgroup data. The aging
piBMD value from 30 to 90 years in general population was computed
by using the formulas in each gender (Table 2).
[0023] The formula used to calculate predicted individual BMD
(piBMD) in each gender was:
piBMD(mg/cm.sup.3)=274.03-0.008.times.age.sup.2-1.304.times.age(mg/cc)(R-
=0.99,P<0.001) in females; and
piBMD(mg/cm.sup.3)=272.99-1.772.times.age(R=0.99,P<0.001) in
males.
[0024] The BMD of the 30 year old group (yBMD) in both genders was
defined as a `standard` for the young women and men. The common
standard deviation (SD) of piBMD from 30 to 90 years in both gender
were calculated.
[0025] The value of yBMD in the young group (30 years) was 221.9
mg/cm.sup.3 in females and 215.2 mg/cm.sup.3 in males. The mean
standard deviation (SD) of both genders was 36 (in female) and 32
(in male) mg/cm.sup.3. The T score formula by the TQCT measurement
with the CAC scan was derived based on the young piBMD and the SD.
T score=(individual mBMD-221.9)/36 in females; T score=(individual
mBMD-215.2)/32 in males. The Z score of mBMD in general individual
was calculated by the formula Z score=(individual mBMD-individual
piBMD)/36 (or 32) in female or male respectively. In comparing the
young group, a T score value of less than 2.5 is osteoporosis in
any aging groups. The Z score value can be used to estimate
osteoporosis in any aging group.
[0026] The measured thoracic BMD in each subject was significantly
higher than the LQCT measurement (by 20.7% in females and 17.0% in
males, P<0.001). A significant positive correlation was found to
exist between the TQCT and the LQCT measurements (R>0.84,
P<0.001). Based on the foregoing, it was determined that a
modified formula for T score measurement by TQCT, which is
comparable to the T score obtained by the LQCT, was needed.
[0027] The TQCT formulas can be used to measure BMD with the CAC
scan directly, while in patients with a previous LQCT-BMD study, a
modified TQCT formula can be used to obtain comparable T score
value with prior study. Due to significant difference in thoracic
and lumbar BMD value and loss rate per year, therefore, there is
significant difference in T and Z score measured by TQCT and
LQCT.
[0028] The QCT technique is a method to measure the bone CTHU and
translate the CTHU to mg/cm.sup.3. The translating function is
performed by the plugs of calibration phantom. The other function
of the calibration phantom is correcting the variation in
inter-scans, inter-objects, inter-scan protocols commonly. The
variation in inter-scan is more important than others. The
techniques disclosed herein allow for the measurement of the
thoracic spine CTHU followed by translation to mg/cm.sup.3 in a
patient scan without the calibration phantom by using formulas.
[0029] FIG. 1 shows an arrangement of a computed tomography (CT)
system. The CT system may be an X-ray CT device including gantry
unit 100 and computing device 101. Although an X-ray CT device is
described herein, it is further contemplated that the CT device may
be an electron beam CT. Gantry unit 100 is designed to acquire
projection data associated with a subject to be examined. Gantry
unit 100 includes X-ray tube 102 and X-ray detector 104. X-ray
detector 104 may be a 64-row multi-slice type detector (multi-row
type detector) which covers the heart area. In other embodiments, a
single-slice type detector (single-row detector) may be used as
X-ray detector 104.
[0030] X-ray tube 102 and X-ray detector 104 may be mounted on a
ring-shaped rotating frame 104 which is rotated/driven by gantry
driving unit 110. In one embodiment, the rotation axis of rotating
frame 104 is defined as the Z-axis. In a rotating coordinate system
centered on the Z-axis, an axis perpendicular to the Z-axis which
connects the focal point of X-ray tube 102 and the center of the
detection surface of X-ray detector 104 is defined as the X-axis.
The Y-axis is perpendicular to both the Z-axis and the X-axis.
[0031] An opening portion is formed in both the central portion of
rotating frame 104 and the housing. In imaging operation, a subject
114 placed on top 120 of support unit 116 is inserted into the
opening portion.
[0032] A high voltage generator 108 applies a tube voltage (high
voltage) between the cathode and the anode of X-ray tube 102. The
high voltage generator 108 also supplies a filament current to the
filament of X-ray tube 102. X-rays are generated from X-ray tube
102 by the application of the tube voltage and the supply of the
filament current.
[0033] X-ray detector 104 may have a plurality of X-ray detection
elements. Data acquisition unit 112 generally called a DAS (Data
Acquisition System) converts a signal output from X-ray detector
104 for each channel into a voltage signal, amplifies it, and
further converts it into a digital signal. This data (also called
pure raw data) is supplied to computing device 101 placed outside
gantry 100. Computing device 101 may be any computing device
capable of performing program execution such as a desktop, laptop,
handheld, server or other similarly suitable type of wired or
wireless computing device.
[0034] Pre-processing unit 124 of computing device 101 performs
pre-processing such as sensitivity correction for the pure raw data
output from data acquisition unit 112. The pre-processed pure raw
data is called raw data or projection data. In this case, such data
will be genetically called projection data.
[0035] Projection data may be stored in storage unit 126 while
codes representing a view representing the rotation angle of X-ray
tube 102 at the time of data acquisition, a row number, and the
position of top 120 are associated with each other. Although this
embodiment will exemplify a case wherein projection data obtained
by helical scanning is processed, dynamic scanning is further
contemplated.
[0036] Storage unit 126 may further include a machine-readable
storage medium (or more specifically a computer-readable storage
medium) on which is stored one or more sets of instructions
embodying any one or more of the methodologies or functions
described herein. During execution thereof by computing device 101,
processing unit 130 may also constitute machine-readable storage
media.
[0037] The machine-readable storage medium may also be used to
store the instructions for determining thoracic vertebral bone
mineral density. While the machine-readable storage medium is
discussed in an exemplary embodiment to be a single medium, the
term "machine-readable storage medium" and also "computer-readable
medium" should be taken to include a single medium or multiple
media (e.g., a centralized or distributed database, and/or
associated caches and servers) that store the one or more sets of
instructions. The terms "machine-readable storage medium" and
"computer-readable medium" shall also be taken to include any
medium that is capable of storing or encoding a set of instructions
for execution by the machine and that cause the machine to perform
any one or more of the methodologies of the present invention. The
terms "machine-readable storage medium" and "computer-readable
medium" shall accordingly be taken to include, but not be limited
to, solid-state memories, and optical and magnetic media.
[0038] In addition to pre-processing unit 124 and storage unit 126,
computing device 101 may include scan control unit 122, image
reconstruction processing unit 128, processing unit 130, image
storage unit 132, display unit 134 (The workstation to measure BMD
of 3T and the coronary calcium score), and system control unit 136.
Image reconstruction processing unit 128 performs image
reconstruction on the basis of the projection data detected by
X-ray detector 104. Image reconstruction processing unit 128
combines projection data of a plurality of heartbeats corresponding
to a set cardiac phase to perform reconstruction, thereby
displaying an image corresponding to the cardiac phase.
[0039] FIG. 2 is a flowchart illustrating one embodiment of a
method for determining thoracic bone mineral density. In this
embodiment, a scan of the heart is taken using a cardiovascular
scanner capable of generating high-resolution images (block 202).
Suitable scanners may include, but are not limited to, an electron
beam tomography (EBT) scanner provided by GE Imatron or other
cardiovascular CT scanners provided by GE, Siemens, Toshiba and
Philips and other manufacturers. Such scanners can freeze the heart
motion with a prospective EKG trigger technique at mid diastole
with a lower radiation dose and higher temporal resolution
images.
[0040] After completing the heart scan, an axial image is
reconstructed by using a field of view size in 35-40 cm for
enclosing the heart and thoracic vertebrae in the same chest image
(block 204). The axial images are transferred to a quantitative
computed tomography (QCT) and cardiac workstation computing device.
In some embodiments, the axial image is reconstructed at the
computing device.
[0041] In some embodiments, the BMD of three thoracic spines 3T is
determined (block 208) and/or a coronary artery calcium score is
completed using the calculation disclosed herein (block 218).
[0042] The computing device may measure the BMD of three thoracic
spines (3T) beginning at the left main coronary artery (block 208).
Representatively, three kinds of images can be displayed in the QCT
computing device, namely axial, sagittal and coronal images. The
level of left main coronary artery is displayed by adjusting a
height from sagittal or coronal images (FIG. 4 displays an axial
image). Once the level of the left main coronary artery is found in
the image, the cursor line is placed at the spine center (FIG. 4
displays a sagittal image). The center of the spine trabecular and
plugs of calibration phantom can be found automatically by the QCT
computing device. The CT Hounsfield unit (HU) and mg/cm.sup.3 can
be displayed automatically by the computing device.
[0043] A first BMD measurement is taken at the spine level
beginning at the main coronary artery. A second BMD measurement is
taken at the spine following the spine level beginning at the main
coronary artery. Finally, a third BMD measurement is taken at the
spine following the first two spines. The thickness of the region
of interest (ROI) is 6 mm or 10 mm and the center of ROI was
located at the center of the vertebrae at a 2-3 mm distance from
the spinal cortical bone. The cortical bone, area with large venous
vessel, islanded bone and calcifying herniated disk were excluded
as much as possible from the ROI by using the free tracing
protocol.
[0044] The mean BMD value of (3T) the three measured thoracic
spines in general population based on two aging intervals in each
gender are listed in table 1:
TABLE-US-00001 TABLE 1 The profile of 30 aging groups in general
population Age range Female Male (year) Mean age Number Mg/cm.sup.3
Mean age Number Mg/cm.sup.3 30 30 42 221.9 30 53 215.2 31-32 31.5
42 217.3 31.5 51 216.6 33-34 33.5 38 215.7 33.5 55 215.1 35-36 35.5
35 215.7 35.6 66 210.0 37-38 37.5 39 213.0 37.5 58 207.1 39-40 39.5
42 211.9 39.6 99 206.0 41-42 41.4 56 209.9 41.6 119 206.8 43-44
43.6 89 208.5 43.5 152 200.2 45-46 45.5 118 207.6 45.5 197 193.2
47-48 47.6 128 199.2 47.6 234 188.6 49-50 49.6 160 197.2 49.5 286
184.5 51-52 51.6 213 190.5 51.5 298 176.9 53-54 53.5 242 181.1 53.5
364 176.1 55-56 55.6 277 174.3 55.5 374 173.2 57-58 57.5 252 166.6
57.5 354 165.8 59-60 59.5 201 165.1 59.5 351 165.9 61-62 61.5 264
157.4 61.5 281 162.5 63-64 63.5 263 154.5 63.5 283 160.3 65-66 65.5
257 153.5 65.5 303 154.7 67-68 67.5 222 148.4 67.5 251 154.7 69-70
69.5 196 143.3 69.5 256 151.6 71-72 71.4 240 137.3 71.6 189 148.1
73-74 73.5 168 131.8 73.5 189 144.3 75-76 75.5 149 126.1 75.5 165
137.2 77-78 77.5 111 125.3 77.6 137 133.4 79-80 79.5 97 117.2 79.4
103 133.5 81-82 81.5 78 109.4 81.4 68 132.6 83-84 83.6 52 108.5
83.5 61 124.9 85-86 85.5 31 109.7 85.6 44 120.5 87-90 88.4 24 102.8
88.9 13 116.0
[0045] Based on the measured BMD data, the predicted general
individual BMD formula is computed (piBMD) (block 210). The formula
used to calculate aging predicted BMD (piBMD) in each gender may
be: piBMD
(mg/cm.sup.3)=274.03-0.008.times.age.sup.2-1.304.times.age (mg/cc)
(R=0.99, P<0.001) in females; =272.99-1.772.times.age (R=0.99,
P<0.001) in males. The piBMD in general population in each
gender is computed and listed in Table 2 below.
TABLE-US-00002 TABLE 2 The profile of predicted BMD (piBMD,
mg/cm.sup.3) in the general population Age(year) Female male Age
Female male 30 227.6 219.8 61 164.3 164.9 31 225.8 218.0 62 162.0
163.1 32 224.0 216.3 63 159.7 161.3 33 222.2 214.5 64 157.4 159.6
34 220.3 212.7 65 155.0 157.8 35 218.5 210.9 66 152.7 156.0 36
216.6 209.6 67 150.3 154.3 37 214.7 207.4 68 147.9 152.5 38 212.8
205.6 69 144.5 150.7 39 210.8 203.8 70 143.0 148.9 40 208.9 202.1
71 140.6 147.2 41 206.9 200.3 72 138.1 145.4 42 205.0 198.5 73
135.7 143.6 43 203.0 196.7 74 133.2 141.9 44 201.0 195.0 75 130.7
140.1 45 198.9 193.2 76 128.1 138.3 46 196.9 191.5 77 125.6 136.5
47 194.8 189.7 78 123.0 134.8 48 192.8 187.9 79 120.4 132.9 49
190.7 186.1 80 117.9 131.2 50 188.6 184.4 81 115.2 129.5 51 186.4
182.6 82 112.6 127.7 52 184.3 180.8 83 110.0 125.9 53 182.2 179.1
84 107.3 124.1 54 180.0 177.3 85 104.7 122.4 55 177.8 175.5 86
102.0 120.6 56 175.6 173.7 87 99.3 118.8 57 173.4 171.9 88 96.5
117.1 58 171.1 170.2 89 93.8 115.3 59 168.9 168.4 90 91.4 113.5 60
166.6 166.7 30-90 164.1 166.7
[0046] In T score calculating, the mBMD of the 30 year old group in
both genders was defined as a `standard` for the young women and
men. In Z score measuring, the predicted individual BMD (piBMD)
value of each aging group is the `reference` value. The standard
deviation (SD) of piBMD from 30-90 years in both gender groups was
calculated, and adjusted (to obtain similar T scores to that
obtained by scanning the lumbar region), as a factor to calculate T
and Z score.
[0047] The value of yBMD in the young sample group (30 years) was
calculated (block 212). The yBMD value was found to be 221.9 in
females and 215.2 mg/cm.sup.3 in males. The standard deviation (SD)
of both gender groups was 36 (in female) and 32 (in male)
mg/cm.sup.3.
[0048] Next, T and Z scores were calculated (block 214). The T
score is a comparison of a person's yBMD to that of a healthy 30
year old of the same sex and ethnicity. The Z score is a number of
standard deviations a patient's BMD differs from the average BMD of
others of their same age, sex and ethnicity. The T score formula
for the TQCT measurement with the CAC scan was derived based on the
ymBMD and the SD. In one embodiment, T score=(individual
mBMD-221.9)/36 in females; T score=(individual mBMD-215.2)/32 in
males. The Z score of mBMD in a general individual was calculated
by the formula Z score=(individual mBMD-piBMD)/36 (or 32) in female
and male respectively. From the T and Z scores calculated, the bone
status of the subject is estimated (block 216). Representatively,
comparing the young group, a T score value of less than -2.5 is
considered osteoporosis in any aging groups and a T score of less
than -1 is considered osteopenia. The Z score value can be used to
estimate osteoporosis in any aging group. These results are
illustrated by FIG. 6A and FIG. 6B.
[0049] The modified formulas were generated in both genders, which
are used to translate the TQCT value to closed LQCT value in
patients with prior LQCT studies and used in connection with the
method illustrated in FIGS. 2 and 3. LQCT T score=0.8789.times.TQCT
T score+0.2688 in females; LQCT T score=0.8139.times.TQCT
score+11.822 in males
[0050] As previously discussed, coronary calcium score may also be
determined (block 218). In some embodiments, the traditional
Agatston score method is used (block 220). Using the Agatston
formula,
score=calcium lesion area mm.sup.2.times.peak density scale (CTHU,
in 1, 2, 3, and 4), 1--CTHU 130-200, 2--CTHU 201-300, 3--CTHU
301-400 and 4--CTHU >400.
Volume(mm.sup.3)=Area(mm.sup.2).times.thickness(mm)
[0051] In some embodiments, a Budoff score method is used (block
222). The Budoff score method refers to the novel score method
disclosed herein. The Agatston score is stepwise, which can reduce
the rescan, interscanner and interindividaul reproducibility. The
peak CTHU cannot represent the total lesion density optimally. For
those reasons, a new scoring system, the Budoff scoring method, was
created. In this scoring system, the mean (not peak CTHU) CTHU/100
is used as the calcium lesion density scale, The Budoff score=area
(mm.sup.2).times.mean CTHU/100, or CAC foci volume/slice
thickness.times.mean CTHU/100.
[0052] In some embodiments, a calcium mass calculation is performed
(blocks 224, 226). The calcium lesion mass (mg) formula is:
volume(mm.sup.3).times.density of CaHA(mg/mm.sup.3)
[0053] the density represented by calibration factor.
[0054] In traditional CAC foci mass measurement, the density value
is estimated, not calculated with use of a calibration phantom.
Others used the formula induced by calibration phantom. In this
score system, the calibration factor (CF, mg/cc/CTHU) of
calibration phantom plugs (displayed on FIG. 5) is used to
translate the CTHU to mg/mm.sup.3 of calcium foci, like BMD
measurement, a given Foci Mass=CF.times.volume (mm.sup.3).
[0055] For patients with a traditional calibration phantom, the BMD
formula is CTHU.times.AF, calculated from the phantom plugs or by
the ratio of CTHU/mg/cc (BMD=CTHU/ratio).
[0056] FIG. 3 is a flowchart illustrating one embodiment of a
method for determining thoracic bone mineral density. The method
illustrated in FIG. 3 is similar to the method disclosed in
reference to FIG. 2, except that the scan is performed without a
calibration phantom (block 304). An image is reconstructed from the
scan data (block 304). Once reconstructed, the thoracic spine and
heart image are displayed (block 306).
[0057] In some embodiments, the BMD of three thoracic spines 3T is
determined (block 308) and/or a coronary artery calcium score is
completed using the calculation disclosed herein (block 318).
[0058] The computed tomography Hounsfield unit (CTHU) of three
thoracic spines (3T) is measured (block 308). In this aspect, a
first spine CTHU measurement is taken at the spine level beginning
at the main coronary artery. A second CTHU measurement is taken at
the spine level beginning at the main coronary artery. Finally, a
third CTHU measurement is taken at the spine following the first
two spines. Next, CTHU is translated to mg/cm.sup.3 (block 310) by
the ratio of CTHU/mg/cc displayed on table 5 (if using a new
calibration phantom, see FIG. 5) or by the ratio of phantom plug
with 150 mg/cc (or mean of 100-200 mg/cc). According to the
technique disclosed herein, the thoracic spine CTHU can be measured
by a variety of scanners then translated to mg/cm.sup.3.
[0059] In EBT scanner, the location of fixed X-ray target is under
table with range angle of 210.degree., this design inducing more
X-ray dose receipted by phantom (reference) area and significantly
higher CTHU than the spine. Therefore, the BMD by EBT is lower than
MDCT in the same individual. One hundred and fifty six cases who
underwent CAC study by both EBT and 64-row detector GE scanner
(VCT, GE Healthcare, Milwaukee, Wis.) on the same day were used to
compare and normalize the BMD values between scanners. In comparing
the mBMD value of both scanners (EBT and MDCT-GE64), there was an
average underestimation of 18% as measured by EBT as compared to
the GE scanner. Currently, most QCT and cardiac studies are
performed using MDCT scanners. To normalize the EBT C300 and C150
scanner) to the MDCT, we used the following formula (Y=1.082
X+12.5, R=0.97). In EBT eSpeed scanner, the translating Formula is
Y=1.1 X.
[0060] Formulas for translating the CTHU values for each of the
different types of scanners are listed below. One can use the
formulas or use calibrating factor (CF) to calculate BMD
(BMD=spinal HU.times.CF) or CAC mass score (=CAC foci mean
HU.times.CF) on phantom less CAC images. [0061] C100: y=0.9+13.11,
R=0.97, n=344, 130kVp, Calibrating factor=0.99 [0062] eSpeed:
Equivalent value with GE scanner=0.98.times.HU (by eSpeed
scanner)+2.86 (mg/cm.sup.3), R=0.98, n=330, 130 kVp, Calibrating
factor=0.86 [0063] C150: Equivalent value with GE
scanner=0.95.times.HU (by C150 scanner)+7.34 (mg/cm.sup.3), R=0.99,
n=3701, 130 kVp, Calibrating factor=0.84 [0064] C300: Equivalent
value with GE scanner=0.9.times.HU (by C300 scanner)+14.3
(mg/cm.sup.3), R=0.97, n=1959, 130 kVp, Calibrating factor=0.83 For
multiple detector CT scanners, the Formula, calibrating factor was
listed on Table 4:
TABLE-US-00003 [0064] TABLE 4 Calibrating factor and calculation
formula with CTHU in various MDCT scanners Scaner and ditector NO
CF Formula R value kVP Philips 256 186 0.874 y = 0.855x + 3.088
R.sup.2 = 0.965 120 Philips 64 200 1.006 y = 0.888x + 2.959 R.sup.2
= 0.994 120 Philips 16 210 0.982 y = 0.937x + 5.570 R.sup.2 = 0.993
140 Toshiba 320 200 0.906 y = 0.929x - 4.718 R.sup.2 = 0.995 135
Toshiba 64 170 0.914 y = 0.904x R.sup.2 = 0.978 135 Toshiba 16 200
0.973 y = 0.983x + 4.065 R.sup.2 = 0.986 135 HEHD 64 194 0.91 y =
0.860x + 7.588 R.sup.2 = 0.991 120 Ge 64 185 0.923 y = 0.889x +
5.648 R.sup.2 = 0.991 120 Ge 16 244 0.804 y = 0.829x - 1.859
R.sup.2 = 0.992 120 Siemens Dual 195 1.031 y = 0.967x + 7.772
R.sup.2 = 0.952 120 Siemens 64 216 0.954 y = 0.934x + 5.723 R.sup.2
= 0.989 120 Siemens 16 180 0.975 y = 0.962x + 2.676 R.sup.2 = 0.995
140
[0065] The value of yBMD in the young sample group (30 years) was
calculated (block 312). The yBMD value was found to be 221.9 in
females and 215.2 mg/cm.sup.3 in males. The standard deviation (SD)
of both gender groups was 36 (in female) and 32 (in male)
mg/cm.sup.3.
[0066] Next, T and Z scores were calculated (block 314). The T
score is a comparison of a person's yBMD to that of a healthy 30
year old of the same sex and ethnicity. The Z score is a number of
standard deviations a patient's BMD differs from the average BMD of
others of their same age, sex and ethnicity. The T score formula
for the TQCT measurement with the CAC scan was derived based on the
ymBMD and the SD. In one embodiment, T score=(individual
mBMD-221.9)/36 in females; T score=(individual mBMD-215.2)/32 in
males. The Z score of mBMD in a general individual was calculated
by the formula Z score=(individual mBMD-piBMD)/36 (or 32) in female
and male respectively. From the T and Z scores calculated, the bone
status of the subject is estimated (block 316). Representatively,
comparing the young group, a T score value of less than -2.5 is
considered osteoporosis in any aging groups and a T score of less
than -1 is considered osteopenia. The Z score value can be used to
estimate osteoporosis in any aging group.
[0067] As previously discussed, coronary calcium score may also be
determined (block 318). The Agatston score method (block 320),
Budoff score method 322 and/or calcium mass calculation (block 324)
may be used as previously discussed in reference to FIG. 2.
[0068] FIG. 4 illustrates an image displayed by a computing device
(workstation computer). The left and right panels of FIG. 4
illustrate an axial image and a sagittal image. From this image,
BMD measurements as described herein can be made.
[0069] FIG. 5 illustrates a calibration phantom with 11 plugs
containing calcium hydroxyapatite (CaHA) in various density. Left 5
circles are CAC Budoff score calibration phantom: Consists of
various dense (130, 200, 300, 400 and 600 mg/cm.sup.3 of CaHA or
Human bone tissue) with the Agatston value in 2.5, 7.5 and 50
closely. Right 6 circles are BMD and Liver calibration phantom: the
BMD phantom consists of various dense of plugs containing human
nature bone or CaHA with 0, 50, 100, 200,400 mg/cm.sup.3. The liver
phantom with a liver dense (60 CTHU measured by GE 64 scanner with
120 kVp and 50 mAs) with 0 CaHA, made by human soft tissue or other
material. Currently two kinds of calibration phantoms are commonly
used: phantom 1 has three plugs containing CaHA in 0, 75 and 150
mg/cm.sup.3 and 12 inches in length and phantom 2 has 4 plugs
containing CaHA in 0, 50, 100, 200 mg/cm.sup.3 respectively (Image
analysis, Columbia, Ky.).
[0070] To perform LQCT studies, an image with a calibration phantom
under patient's back is scanned, the plugs densities (CTHU) are
detected by computer, and the formula to translate CTHU to mg/cc is
computed individually. Two shortcomings of commonly used
calibration phantoms are: (1) the range of phantom plugs containing
CaHA does not cover the common BMD values found in the thoracic
spine; and (2) the ratio of HU/mg/cc varies significantly
throughout the length of the spine. Theoretically, the optimal
translation method is using the ratio (HU/mg/cc) of a given phantom
plug to correct the spine BMD that closed in HU with used plug.
[0071] To design an optimal plug size of calibration phantom, we
have obtained the BMD contribution of thoracic spine vertebrae in
9807 general population undergoing CAC scans displaying in
following Table 5.
TABLE-US-00004 TABLE 5 The distribution of general population
Distribution of 9807 population 22-90 ys mg/cc no Percent (%)
Phantom 20-50 22 0.2243 30 51-100 673 6.8624 75 101-150 3148 32.1
125 150-200 3730 38.034 175 201-250 1783 18.181 225 251-300 392
3.9971 300 301-350 54 0.5506 >350 5 0.051 sum 9807 100
[0072] According to these values, the 6 plugs can be used to make a
new phantom, there are plugs containing the various concentration
of CaHA displayed in Table 5. The plugs containing 60 mg/cc CaHA
can be used to calibrate the liver. Overall, 99% of thoracic BMD
range can be covered by using the new calibration phantom displayed
in FIG. 5. The benefits of using this new calibration phantom are:
(1) Covering 99% of BMD range of thoracic vertebrae; and (2)
Decrease the calculation error by use of a formula (3). Can be used
to calculate CAC fuci mass score and calibrate CAC score.
[0073] In some embodiments, a new computer system for BMD
measurement is contemplated. The computer system may include a
computer program implemented by a workstation BMD computer. For the
CT image with a new calibration phantom, the program may be used to
perform the following operations: [0074] 1. Detect the CTHU of
calibration phantom plugs and calculating the ratio of HU/mg/cc or
CF (mg/cc/CTHU), [0075] 2. Detect the CTHU of given thoracic spine,
[0076] 3. Translate CTHU to mg/cc of this spine by using the ratio
of plug that is closest to the density of the spine itself. For
example: If the CTHU of a given thoracic spine is 63, the CTHU is
85 at plug containing CaHA in 75 mg/cc, that is close with the 63
hu, the ratio 1.133 (85/75) is 1.333, therefore 63/1.133=55.6 mg/cc
in this spine. Or using CF (CTHU.times.CF)
[0077] In some embodiments, the computer program and a workstation
BMD computer can be used for imaging with a traditional calibration
phantom (0, 75, 150 mg/cc) as follows: [0078] 1. Detect the CTHU of
Plug with 150 mg/cc CaHA and calculate ratio (150-ratio), [0079] 2.
Obtain the ratio of a given spine (G-ratio), G-ratio=150-ratio+D
(difference between a given spine and plug of 150 mg/cc). The
G-ratio can be found from Tables 5 and 6. [0080] 3. Translate HU to
mg/cc at a Given spine, BMD mg/cc=CTHU/G-ratio, or
CTHU.times.CF.
[0081] In other embodiments, the computer program and workstation
BMD computer may be used in patients with a traditional phantom (0,
50, 100 and 200 mg/cc) as follows: [0082] 1. Detect the CTHU of
Plug with 100 and 200 mg/cc CaHA and calculate the 150-ratio
(150-ratio, =mean ratio of 100 and 200-ratio), [0083] 2. Obtain the
ratio of a given spine (G-ratio), G-ratio=150-ratio+D value
(difference between a given spine and plug of 150 mg/cc). The
G-ratio can be find from following table, displayed on [0068] and
[0069]. [0084] 3. Translate HU to mg/cc at a Given spine, BMD
mg/cc=CTHU/G-ratio, or CTHU.times.CF.
[0085] The analysis is the ratio of different density of the spine
in 22,269 patients to establish norms for different scanners for
thoracic vertebra. From this data, the optimal calibration plug
size and calibration method for a computer system is derived. In
Table 6, the value of >400 mg/cc were measured from cortical
bone or calcium foci.
TABLE-US-00005 TABLE 6 Ratio of CTHU/mg/cc in varying BMD range and
scanners C300 ge16 C150 ge64 Simens Toshiba Philips ratio Ratio
ratio ratio ratio ratio bone-hu/mg/cc c100 eSpeed Phantom ratio
Ratio ratio ratio ratio ratio 20-50 mg/cc 1.113 1.175 1.224 1.309
0.845 0.931 0.945 51-100 1.134 1.2 1.22 1.217 0.845 1.0016 0.965
101-150 1.138 1.202 1.211 1.188 1.0345 1.0317 1.006 150-200 1.146
1.202 1.211 1.171 1.0438 1.0427 1.013 201-250 1.202 1.211 1.16
1.0598 1.0434 1.014 251-300 1.202 1.211 1.138 1.073 1.0443 1.014
301-350 1.208 1.211 1.132 1.092 1.0495 1.019 351-400 1.211 1.211
1.1 1.117 1.061 1.021 401-500 1.211 1.211 1.1 1.119 1.07 1.023
501-600 1.211 1.211 1.1 1.121 1.08 1.04 601-700 1.211 1.211 1.1
1.121 1.091 1.04 >701 1.211 1.211 1.1 1.121 1.099 1.04 sum 1.01
1.1 1.133 1.2 1.21 1.21 1.01 1.01 0.99 number 344 330 54 2450 2401
3200 7940 4200 1350
[0086] D values of given spine with varying range of BMD and
scanners were obtained from Table 6 (D value=a G-ratio-C150-ratio),
C150-ratio is the value of ratio in spine with the dense in 150
mg/cc of phantom plug.
TABLE-US-00006 TABLE 7 D values (a G-ratio-C150-ratio) in varying
BMD range and scanners c300 GE16 C150 ge64 Simens Toshiba philip
Ratio Ratio Ratio Ratio Ratio Ratio Ratio mg/cc D value D value D
value D value D value D value Dvalue 20-50 -0.03 0.013 0.128
-0.1948 -0.1038 -0.068 -0.025 51-100 -0.002 0.009 0.036 -0.1948
-0.0332 -0.049 -0.004 101-200 (150) 0 0 0 0 0 0 0 201-250 0 0
-0.021 0.02 0.0086 0.007 0.008 251-300 0 0 -0.043 0.0332 0.0095
0.007 301-350 0 0 -0.049 0.0522 0.0147 0.012 351-400 0.006 0 -0.081
0.0772 0.0262 0.014 401-500 0.009 0 -0.081 0.0792 0.0352 0.016
501-600 0.009 0 -0.081 0.0812 0.0452 0.033 601-700 0.009 0 -0.081
0.0812 0.0562 0.033 >701 0.009 0 -0.081 0.0812 0.0642 0.033
[0087] In some embodiments, the computer program and a workstation
BMD computer may be used in patients without calibration phantom.
The system can detect the CTHU of mid trabecula of 3T in 6 mm
thickness automatically. The system then translates CTHU to mg/cc
by the ratio in varying scanners: CTHU/G-ratio, displayed on Table
6, or by formulas previously discussed.
[0088] A device, such as device 101, for performing the operations
herein may be specially constructed for the required purposes or it
may comprise a general purpose computer selectively activated or
reconfigured by a computer program stored in the computer. Such a
computer program may be stored in a computer readable storage
medium, such as, but not limited to, any type of disk including
floppy disks, optical disks, CD-ROMs and magnetic-optical disks,
read-only memories (ROMs), random access memories (RAMs), EPROMs,
EEPROMs, magnetic or optical cards, Flash memory devices including
universal serial bus (USB) storage devices (e.g., USB key devices)
or any type of media suitable for storing electronic instructions,
each of which may be coupled to a computer system bus.
[0089] The algorithms and displays presented herein are not
inherently related to any particular computer or other apparatus.
Various general purpose systems may be used with programs in
accordance with the teachings herein or it may prove convenient to
construct a more specialized device to perform the described
method. In addition, the invention is not described with reference
to any particular programming language. It will be appreciated that
a variety of programming languages may be used to implement the
teachings of the invention as described herein.
[0090] A computer readable medium includes any mechanism for
storing information in a form readable by a computer. For example,
a computer readable medium includes read only memory ("ROM"),
random access memory ("RAM"), magnetic disk storage media, optical
storage media, flash memory devices or other type of
machine-accessible storage media.
[0091] In the preceding detailed description, specific embodiments
are described. It will, however, be evident that various
modifications and changes may be made thereto without departing
from the broader spirit and scope of the claims. The specification
and drawings are, accordingly, is to be regarded in an illustrative
rather than restrictive sense.
* * * * *