NASA CASE NO. I__M_L1JSD_D_IPRINT FIG. J ___

The invention disclosed in this document resulted from research in aeronautical

and space activities performed under programs of the National Aeronautics and Space

Administration. The invention is owned by NASA and is, therefore, available for

licensing in accordance with the patent licensing regulations applicable to U.S.

Government-owned inventions (37 CFR 404.1 et seA.).

To encourage commercial utilization of NASA-owned inventions, it is NASA

policy to grant licenses to commercial concerns.

nonexclusive licensing to promote competition and

Although NASA encourages

achieve the widest possible

utilization, NASA will provide the necessary incentive to the licensee to achieve early

practical application of the invention.

Address informational requests for this invention to the Technology

Applications Team, NASA Langley Research Center, Code 200, Hampton, Virginia

23681-0001.

Address applications for license to the Patent Counsel Office, Mail Stop 212,

3 Langley Boulevard, Hampton, Virginia 23681-0001.

! ( ,_

Serial No.: 08/592,833

Filed: 01/26/96 LaRC
LAR- 1 5 040- 1 AWARDS ABSTRACT 

METHOD OF AND APPARATUS FOR 

HISTOLOGICAL HUMAN TISSUE CHARACTERIZATION 

USING ULTRASOUND 

The present invention relates generally to the medical classification of human tissue as healthy or 

unhealthy. More specifically, the invention uses ultrasound for determining histological 

characteristics of tissue by converting the return energy pulses into numerical terms, thus 

facilitating a quantitative analysis for medical diagnosis. 

A method and apparatus for determining important histological characteristics of tissue, including 

a determination of the tissue's health. Electrical pulses are converted into meaninel numerical 

representations through the use of Fourier Transforms. These numerical representations are then 

used to determine important histological characteristics of tissue. This novel invention does not 

require rectification and thus provides for detailed information from the ultrasonic scan. 

Inventor: 

Address: 

Employer: 

Inventor: 

Address: 

Employer: 

William T. Yost 

797 Fawn Lane 

John H. Cantrell 

101 Tuckahoe Trace 

George Taler 

3909 Juniper Road 

Baltimore. MD 2121 8 

Initial Evaluator: Eric I. Madaras 

Serial No. : 081592,833 

Filed: 1/26/96 
LAR 15040-1 -1- PATENT APPLICATION

METHOD OF AND APPARATUS FOR

HISTOLOGICAL HUMAN TISSUE CHARACTERIZATION

USING ULTRASOUND

5 Origin of the Invention

10

The invention described herein was jointly made by employees of the United

States Government and an employee of the University of Maryland Medical School. It

may be used by and for the Government for governmental purposes without the

payment of any royalties thereon or therefor.

Background of the Invention

15

20

.

m

Technical Field of the Invention

This invention relates to the medical classification of human tissue as healthy or

unhealthy. More specifically, the invention uses ultrasound for determining

histological characteristics of tissue by converting the return energy pulses into

numerical terms, thus facilitating a quantitative analysis for medical diagnosis.

. Discussion of the Related Art

25

Ultrasound has routinely been used in the medical profession to determine the

shape, size and thickness of human tissue. Historically, this has been achieved through

the detection of specular reflections from macroscopic tissue interfaces. Although this

method allows for a general characterization of the tissue, it does not reveal its

underlying health and structure. In order to obtain such a detailed analysis, reflections

from the microscopic interfaces (scatterers) contained within the tissue must also be

detected. An improved invention to detect these scatterers has yet to be discovered.
LAR 15040-1 -2- PATENT APPLICATION

The prior art is able to determine general characteristics of tissue from its

macroscopic interface reflections. This is commonly determined by transforming

analog ultrasonic radio frequency data into a visual display. This technique requires

the expertise of a skilled operator to interpret the display which does not include an

5 accurate determination of the underlying pathology of the tissue.

Other prior art systems use Fourier Transforms to detect microscopic

reflections; however, these systems do not allow for direct measurement of reflectance

through self-calibration, and therefore are subject to calibration problems. These

methods separate the components of an ultrasonic pulse into corresponding

I0 frequencies, using the Fourier Transform. This requires a reference plate to normalize

the Fourier energy from the reflected tissue and thus the accuracy and range of

available data is limited.

Similarly, the prior art taught by Sommer, Joynt, Carroll and Macovski

("Ultrasound characterization of abdominal tissues via digital analysis of backscattered

15 wavefronts", Radiology, ] 41:81 ]-7, ]98 I) uses a Fourier analysis to determine the

mean spacing of scatterers in the liver and spleen. This method, however, does not

provide for the determination of key variables that give ranges for specific tissues and

their state of health.

U.S. Pat. No. 5,417,215 of Evans et al. provides a method of interpreting the

20 microscopic interfaces which requires demodulating the return energy pulses by fullwave rectification to obtain the amplitude modulation of the pulses and computing the

power spectrum by performing a Fast Fourier Transform on the rectified, digitized

pulses. The requirement of rectification limits this method in providing information

from the ultrasonic scan. It does not provide specific, well established physical

25 parameters of the body tissue under investigation. It requires the comparison of

Fourier energies or ratios, as well as, comparisons based on correlations.

It is, therefore, an objective of the invention to provide an improved ultrasound

tissue characterization system for histological tissue classification.

It is a further objective of the invention to provide a system which does not

30 require rectification, thereby allowing a more detailed analysis.
LAR 15040-1

Summary_ of the Invention

-3- PATENT APPLICATION

The present invention converts electrical pulses into meaningful numerical

representations through the use of Fourier Transforms. This information can be used to

determine important histological characteristics of tissue, including a determination of

the tissue's health. This novel invention does not require rectification and thus

provides for a much more detailed information from the ultrasonic scan.

10

15

Brief Description of the Drawings

FIG. 1 is an equipment diagram for data taking;

FIG. 2 is an illustration of an ultrasonic wave passing through an iterated

structure constructed from two acoustically different tissue types;

FIG. 3 is a typical ultrasonic echo pattern received from tissue reflections;

FIG. 4 is a plot of the Fourier Transform equation with arbitrary amplitude; and

FIG. 5 is a plot of the Fourier Transform equation with discrete interpolation.

Detailed Description of the Invention

20 Referring more particularly to the drawings, a well-damped 10MHz transducer

one-eighth inch (1/8") diameter crystal 12 is connected to a wide band pulser-receiver

14. The pulser-receiver 14 is a sonic generator and receiver for generating, sending

and receiving waves. The wide-band (non-rectified) output of the pulser-receiver 14 is

connected to a digital oscilloscope 16, which has a plotter 18 connected to it to record

25 the data output. The oscilloscope 16 provides live visual reading of the output. The

data-point plotter 18 gives a graphic reading of the output. The oscilloscope 16 also

has Fast Fourier Transform capability.

The transducer 12 emits an ultrasonic pulse that travels through the body 20

into the subcutaneous tissue that is under examination. This tissue reflects a sequence

30 of small amplitude echoes back to the transducer 12. The sequence of echoes from the
LAR 15040-1 -4-

tissue is received by the transducer 12, which converts the ultrasonic pulse sequence

into a sequence of electrical pulses. The electrical pulse sequence is amplified by the

wide-band amplifier in the pulser-receiver 14 and sent to the oscilloscope 16 for

measurement. The oscilloscope 16, further processes the data, displays it on a visual

5 monitor, and sends it to a plotter 18 for a hard-copy record. The oscilloscope 16 has

the ability to perform Fast Fourier Transforms on the digitized pulses.

Specifically, the transforming equations used are as follows:

G(f)= f h(t)e-'2=_dt = F[h(t)]

05

PATENT APPLICATION

l(a)

h(t): i G(f)e '2'_df : F[G(f)] l(b)

10 where G(r') is the Fourier Transform of h(t).

The following properties of this type of transform are used:

F[h(t-to) ] = exp(-i2Xfto) F[h(t)] (shift operation) 2(a)

F/ /7

F[ _ hm(t)] = _ F[hm(t)] (addition theorem) 2(b)

m=l m=l

15

1 {

F[h(kt)] = kG(k ) (similarity theorem) 2(c)

here i=_ 2---

Consider the echo train from an alternating stacked sequence of tissues. The following

relationships are used:

Pz/7-t = Po(T12T21) 2(n ORlzeXp(-2n°'lll - 2(11-1)°'212) (odd members) 3(a)
LAR 15040-1 -5- PATENT APPLICATION

P2o -- -P0(7'12T21) 2° 1R12exp(-2n[_lll+_212]) (even members) 3(b)

In examining the echos, each received echo is subscripted with an index to indicate the

temporal order of reception

[zxt ]2

hi(t-to) = Pexp(-_ L jJ )cos2_fo(Atj)

0 2

(4)

where t o marks the reception of the first echo, and Atj is the time interval between the

jth received reflection and the first echo.

By allowing Gj(f)=F[hj(t-t0)] and using (la), (2a) and (3a) the following

relationship is obtained

ol ?0

c;(f) = E%(f)= 2F[h.(t-gl--K(f)F[ho(0] (5)

J=l J=l

" /2

I0 where g(f) = N(7_2Tz,y-'R,zexp(-([j+l]=,l,-[j-l]=J2)-i2r_f([j+l]ll-[j-1]--))-l]

J=l C 1 C2

m 11 12

- E (T, zTzly-lRlzexp(-J[_,I1 +_212]-i2 r_j')[-- +--])

J=l C 1 C2

(6)

It is assumed that the later reflections are small and equation (6) is not greatly affected

by letting m approach infinity, the equation is rewritten:

11 A

R12exp[-2all I - i4_zf--L][1-(T12T21)exp[-2a212 - i4r_j.--z--]]

15 K(/') = cl c2 (7)

/ 1 l,

[l -(T,2T202exp[-2[a_ll+%12]-i4rcf(-- +_)]]

C 1 C2
LAR 15040-1 -6- PATENT APPLICATION

by substituting the sum for each series.

In general, any part of the transform may be used to express a relationship

among the ultrasonic variables and, hence, give useful information about the significant

tissue classifications. For purposes of illustration, the magnitude is used, although the

real part, the imaginary part, the phase or any combination is just as instructive.

Next, the Fourier transform of the incident ultrasonic pulse,

i 2

P--P0exp(-II-2;-)cos2IIfjt 0 is evaluated by substitution into equation l(a)

o"

,4 /2

/q_h°(t)] = -o"J'o P°exp(-'n4) cos (2nfot)dt

(8)

which upon evaluation gives

P0oexp( - _o2(f-fo) 2)

l0 F[ho(t)] -- , (9)

2

Using standard algebraic techniques and trigonometric substitutions the magnitude is

rewritten:

IGff> 0, to=0) I = P°°exp(-_°z(f-f°)2) X

2

1 - 2Tcos(4nft2)exp(-2H2) + (Texp(-2H2)) 2

R12exp-2H I

1 - 2T%os(4nfi,)exp(-ZHo) + (T2exp(-ZH0)) 2

(]0)

15 where fo is the center frequency of the ultrasonic transducer, H o is c_ll I + it212, H l is

c_111,H 2 is t_212, T is (TI2 T21), t2 is 12/c2, ts is I1/c 1 + 12/c2, tt 1 is the attenuation
LAR 15040-1 -7- PATENT APPLICATION

coefficient of the type 1 material, and o_2 is the attenuation coefficient of the type 2

material.

An analysis of equation (10) shows the shape of IG(f>0, t =0)1 is determined by

two different undulations. The more rapid undulation occurs between much smaller

5 frequency intervals, and is determined by the cosine function in the denominator of the

radical.

values

The cosine function, cos 4nil, causes this denominator to vary between the

[1 - (TZexp(-2H0))] 2, and [1 + (T2exp(-2H0))] 2

both values are perfect squares. This occurs when cos4nfl_ varies between +l and -l,

10 for which 4nfl_ = nTv or

2xf, = 1 (11)

C 1 C2

where Af Sis the smaller frequency interval for the more rapid undulation. The

numerator inside the radical also varies between

[1 - (T exp(-2H2))] 2, and [ 1+ (T exp(-2H2))] z

15 but with a frequency of

1

Af2- (12)

(2 2

where Af_ is the frequency of the slower undulation. Solving equations (11) and (12)

for I1 and 12 respectively it is determined:
LAR 15040-1 -8- PATENT APPLICATION

(13a)

C2

(13b)

By measuring the frequency intervals, Af S and Af2, one can determine an average

thickness of a ground substance, lz and the cluster of substantive cells, 11.

The plot of equation (10) reveals a series of maximum and minimum values.

One can trace the envelopes of the relative maxima and minima by noting the

occurrence when cos 4_Zffs= +1 and -1, respectively

]GupperQf>O, to=0)1= A oexp(-na2(f-fo) 2) x

2

R_zexp(_2H 0 V/1-2Texp(-2Hz)cos4nft 2 + (Texp(-2H2)) 2

1 - T2exp(-2H0)

(14)

10 while

IGzower(f>O, t=0)I=

A o exp(- go2OC-fO) 2)

2

X

R_zexp(-2H1) V/1-2 Texp(-2H2)cos4_ft 2 + (Texp(-2H2)) 2

1 + l'Zexp(-2H0)

(15)

For a given frequency, fj (e.g. at a maximum for [Gupper(fl, t=0)l) the ratio,
LAR 15040-1 -9- PATENT APPLICATION

IGupper(fl , Io =0) I 1 + T2exp(-2H0)

= = (16)

IGto,,,er(f l, t0--0) 1-T2exp(-2H0)

Solving for T 2 gives

T 2 1 -R_2 e- 1

= = (_-1-+1 ) exp (2H0) (17)

where ¢ is the ratio of maximum envelope to minimum envelope. Using data

measurements one can obtain the values of¢ as a function of frequency and by curve

fitting obtain values for T and H 0.

In determining the collagen content in the ground substance, equation (17) is

z,-z 2

solved for and RI2- , R_z=-R21 is used to obtain

Z l +Z 2

10

1- I 1-( e-1 ) exp(2Ho)

Z2 = Z1 [ _+1 ]

1 +_ 1 - e+l_----}-1 exp(2Ho)

(18)

15

where Z l is the acoustic impedance of the cluster of fat cells, which is assumed to be

the same as the acoustic impedance of the lipids stored in the fat cell clusters. These

lipids possess a measurable acoustic impedance. Combined with the experimental

determination of e, Z 1 and H 0, Z 2, the acoustic impedance of the ground substance,

can be calculated. This analysis suggests a closer examination of the factors of the

ground substance's acoustic impedance.
LAR 15040-1 -10- PATENT APPLICATION

In determining the collagen and mass density [gms/cm ] of tissues, the

published values of the mass density of pure collagen varies from 1.16 to 1.33.

However, collagen is only one of the many specialized molecular species found in

tissues. Upon examination of the mass densities of the other constituents however it

was discovered that a reasonable mass density model for ultrasonic applications is

essentially a two-component mixture comprised of collagenous and other materials.

Using the definition of mass density and further assuming that the collagen fiber

diameters are smaller than the ultrasonic wavelength in the tissue it can be written

P = 1 (19)

C C

1----

100 100

+

Pl P2

l0 where C is the wet weight percent of collagen, Pl is the density of the non-collagenous

material in the tissue and P2 is the density of the collagenous material.

The sound velocity in a mouse tail tendon fibers has been reported to be

1.733+ 0.056 x 105 cm/sec (Goss and O'Brien, Journal of Acoustical Society of

America, Vol. 65, pages 507-511; 1979). Tendon collagen is 30% wet weight.

15 O'Brien (in "Proceedings Ultrasonic International 77", IPC Science and Technology

Press, Guildford, England, pages 194-205; 1977) has empirically determined that the

velocity of sound in tissue, c, depends upon the percent wet weight of collagen in the

tissue's composition, C, according to the following relation

c -- (1.588 + 0.032 logeC ) x 105 cm/sec (20)

20

The acoustic impedances are calculated to be
LAR 15040-1

Z 2 =

-11-

(1.588+0.032 logeC ) x 105

C C

100 100

+

91 92

PATENT APPLICATION

(21)

gms/cm 2sec

10

15

The measurement and analysis technique gives Z> With equation (21) it is possible to

determine the weight percent of collagen in the ground substance in-vivo if the density

is known of the collagen fibers. But the density of collagen fibers depends in part on

the health and nutrition of the patient. This makes the value ofZ 2 a potentially good

indicator of tissue health with the larger values ofZ 2 indicating more and better grade

collagen in the ground substance. By assuming a reasonable range of values for the

collagen fiber density the determination gives a range of values for the weight percent

of collagen in tissues in-vivo. The linkage is the degradation of the mechanical

properties of these tissues is directly involved with the failure of the tissue's mechanical

properties. That connection is the weight percent of collagen and the collagen's

density (the higher the density, the better its structural properties) in the ground

substance.

Using a curve fitting algorithm for the experimentally determined quantity

(e - 1) (22)

e + 1

Both T 2 and H 0 can be determined by solving the equation

T2exp(_2H0 ) = (e - 1)

8+ 1

(23)

20

where H is eql t + {z212. Since I1 and 12 are determined according to equations 13(a),

13(b) and s t can be estimated from scattering and absorption of ultrasonic waves by

fat cells, one can determine %
LAR 15040-1 -12- PATENT APPLICATION

H o - _Lll

_2 - (24) t2

10

which can be measured as a function of frequency. This information can be used to

assess the quality of collagen fibers and the areal density of the fiber network (weave)

in the ground substance. A correlation with invasive measurements and to a lesser

extent to in vitro measurements will permit the best estimates of these quantities.

In this manner, it is clear that more than a broad classification of healthy or

unhealthy can be realized for smaller regions of interest. Most significantly, a

diagnosis for the development of pressure ulcers can be facilitated through the use of

this invention.

It is specifically intended that the present invention not be specifically limited to

the embodiments and illustrations contained herein, but embrace all such modified

forms thereof as come within the scope of the following claims.

What is claimed is:
LAR 15040-1 -16- PATENT APPLICATION

METHOD OF AND APPARATUS FOR

HISTOLOGICAL HUMAN TISSUE CHARACTERIZATION

USING ULTRASOUND

5 Abstract of the Disclosure

10

A method and apparatus for determining important histological characteristics

of tissue, including a determination of the tissue's health. Electrical pulses are

converted into meaningful numerical representations through the use of Fourier

Transforms. These numerical representations are then used to determine important

histological characteristics of tissue. This novel invention does not require rectification

and thus provides for detailed information from the ultrasonic scan.
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