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Fiducial registration error and target

registration error are uncorrelated

J. Michael Fitzpatrick

J. Michael Fitzpatrick, "Fiducial registration error and target registration error

are uncorrelated," Proc. SPIE 7261, Medical Imaging 2009: Visualization,
Image-Guided Procedures, and Modeling, 726102 (13 March 2009); doi:
10.1117/12.813601

Event: SPIE Medical Imaging, 2009, Lake Buena Vista (Orlando Area),
Florida, United States

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 Fiducial registration error and
target registration error are uncorrelated
J. Michael Fitzpatrick
Dept. of Electrical Engineering and Computer Science,
Vanderbilt University, Nashville, TN 37235, USA

ABSTRACT

Image-guidance systems based on fiducial registration typically display some measure of registration accuracy based on
the goodness of fit of the fiducials. A common measure is fiducial registration error (FRE), which equals the root-mean-
square error in fiducial alignment between image space and physical space. It is natural for the surgeon to regard the
displayed estimate of error as an indication of the accuracy of the system’s ability to provide guidance to surgical targets
for a given case. Thus, when the estimate is smaller than usual, it may be assumed that the target registration error (TRE)
is likely to be smaller than usual. We show that this assumption, while intuitively convincing, is in fact wrong. We show
it in two ways. First, we prove to first order that for a given system with a given level of normally distributed fiducial
localization error, all measures of goodness of fit are statistically independent of TRE, and therefore FRE and TRE are
uncorrelated. Second, we demonstrate by means of computer simulations that they are uncorrelated for the exact
problem as well. Since TRE is the true measure of registration accuracy of importance to the success of the surgery, our
results show that no estimate of accuracy for a given patient that is based on goodness of fiducial fit for that patient gives
any information whatever about true registration accuracy for that patient. Therefore surgeons should stop using such
measures as indicators of registration quality for the patients on whom they are about to operate.
Keywords: Registration, image guidance, fiducial, accuracy, surgery, error analysis

1. INTRODUCTION
In 2000, Steinmeier and colleagues, in an in-vitro investigation into the estimation of registration accuracy displayed by
several fiducial-based neuro-navigation systems, reported that they could find no correlation between the systems’
displayed estimations of registration accuracy and the actual accuracy [1]. Thus, higher than normal estimated accuracies
were not accompanied by higher than normal true accuracies, nor were there correlations for lower than normal values.
The systems’ estimations are made after fiducials that have been localized in a pre-operative image have been physically
localized in the operating room, and thus they have available as input the goodness of fit of the two sets of localizations.
The surprising result that the systems’ estimates are unrelated to truth, suggests that there is an underlying problem with
the method by which these systems predict registration error. The purpose of the work reported here is to show that
predictions of registration accuracy based on goodness of fit are bound to fail and are therefore unreliable.

These systems all employ rigid transformations during the registration process, which for surgical resections involving
bone or involving soft tissue attached to bone, is a reasonable assumption and is not the source of the failure that we
present here. Indeed Steinmeier’s experiments involved only rigid objects. Rigid transformations can be determined via
fiducials that are attached to the anatomy before imaging and remain in place through the registration procedure. The
position of each fiducial is localized in both image space and physical space, and then a transformation from image
space to physical space is chosen that is “optimal” in the sense that it minimizes the fiducial registration error (FRE),
where FRE is the root-mean square of the distance between the localized position of each fiducial as transformed from
image space to physical space and the position of that corresponding fiducial localized in physical space. Because of
FLE, the registration is invariably flawed to some degree, and FRE is a readily available measure of registration error.
Sibson in 1979 [2] investigated the statistical relation between FRE and FLE for the case of isotropic FLE and provided
an expression that can be used to relate their expected squared values as follows:

Medical Imaging 2009: Visualization, Image-Guided Procedures, and Modeling,

edited by Michael I. Miga, Kenneth H. Wong, Proc. of SPIE Vol. 7261, 726102
© 2009 SPIE · CCC code: 1605-7422/09/$18 · doi: 10.1117/12.813601

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 FRE 2 = (1 − 1 2 N ) FLE 2 , (1)
where . means “expected value of ”. Expressions for FRE for each individual fiducial have also recently been derived
[3]. FRE is an easily measured quantity, but it is not as important as target registration error, TRE (for FLE, FRE, and
TRE, we will use boldface when we are denoting the vector displacement), which is the displacement from the true
position of a registered point not used as a fiducial. The target error TRE ( x ) at a point x of interest to the surgeon is the
true measure of registration error. In 1998 and 2001, we investigated the statistical relation between TRE and FLE for
isotropic FLE and provided expressions relating their expected root-mean-square values [4],[5],
1 ⎛ 1 3 d2 ⎞
TRE ( x ) = ⎜ 1 + ∑ k2 ⎟ FLE 2 ,
2
(2)
N ⎝ 3 k =1 f k ⎠
where d k is the distance of x from principal axis k of the fiducial configuration, f k2 is the mean of the squared distances
of the fiducials from that axis. Eq. (1) can be used to estimate the square of FLE from measurements of FRE for many
cases. With this estimate available, Eq. (2) can then be exploited to predict TRE based on the fiducial configuration
when fiducials are used (a) on a patient, (b) on a coordinate reference frame attached to a patient, and (c) on a surgical
probe [6]. For anisotropic FLE, more complex expressions than that of Eq. (2) have recently been derived by Wiles [7]
and Moghari [8].

When a surgeon employs an image-guidance system based on fiducial registration, that system may display the
measured FRE value or an estimate of TRE based on the measured FRE, as an indicator of registration accuracy [9]. The
surgeon will thereby, with experience, become familiar with the typical level of indicated accuracy for a given
procedure. It is common, then, for the surgeon to regard the indicated accuracy for a given patient’s procedure as an
indication of the actual accuracy for that procedure. Thus, for a case in which FRE is smaller than its mean, it is assumed
that target registration error (TRE), which is the true measure of registration accuracy, is also likely to be smaller than
usual, and likewise, when FRE is higher than normal, it is assumed that TRE will be higher than normal.

The purpose of this paper is to show that this intuitively satisfying assumption is wrong. We introduce a new approach to
the statistical analysis of error in fiducial registration and use it to prove that for normally distributed FLE, the values of
FRE and TRE are uncorrelated to first order in FLE and that, in fact, all measures of goodness of fit are statistically
independent of TRE. Then, by means of simulations based on typical fiducial configurations and typical values of FLE,
we show that FRE and TRE are uncorrelated for the exact problem as well. Thus, goodness of fit cannot be used as a
predictor of true registration accuracy. These results in no way detract from previous results relating FRE to FLE or TRE
to FLE, all of which give correct expected values based on expected values for FLE squared. Instead, it is shown here
that a deviation of FRE from its predicted value does not indicate anything about how TRE is likely to have deviated
from its predicted value. In other words, if, for a given registration, FRE is larger or smaller than the value predicted by
Eq. (1), there is no reason to suspect that TRE will be larger or smaller than the value predicted by Eq. (2).

While it may seem intuitive to expect TRE to increase when FRE increases, it is easy to construct counter-examples,
[10],[11], as is shown by Figure 1. Figure 1(a) shows image space, while (b) and (c) show physical space for two
different scenarios. The dotted circles are the positions of the fiducials as localized in image space. The solid circles are
the physical-space localizations. The light gray crosses show the (true) position of a surgical target. The dark gray
crosses show the position to which that target is registered in physical space. In (b) the fiducial localization errors

Figure 1. Examples of FRE versus

TRE. (a) Image space showing three
fiducials (dotted circles) and a target
(cross). (b) Physical space showing a
set of fiducial localization errors that
can be corrected exactly by clockwise
rotation about the “bull’s eye”. TRE
is large, but FRE is zero. (c) Physical
space showing a set of fiducial
localization errors that cannot be
corrected by any rigid transformation.
(a) (b) (c) FRE is large, but TRE is zero.

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 (arrows) are equivalent to a rigid rotation about the “bull’s eye”. This rotation is the optimal transformation. In fact, it
reduces FRE to zero. The rigid transformation in (b) results in the target position (dark cross) being displaced from its
true position (light cross). Thus, in (b) TRE is large, but FRE is zero. In (c) the fiducial localization errors are not
equivalent to any rigid transformation. Instead they are equivalent to a uniform expansion from their mutual centroid.
The result is that the optimal registration produces a perfect target registration but leaves the fiducials badly misaligned.
Thus, in (c) FRE is large, but TRE is zero.

Figure 1 shows schematically that TRE is not necessarily monotonic in FRE. It is easy to construct such examples, but
no example or set of examples can answer the question, “Are the fluctuations of FRE and TRE correlated?” We will now
show that the answer to this question is, “No”. We begin with mathematical derivations and follow them with
simulations.

2. DERIVATIONS
Our derivations are based on a linearization of the rigid, point registration problem. We begin with a statement of the
registration problem.
2.1. The Registration Problem
The fundamental problem of rigid, fiducial registration is to find optimal transformation, which comprises the rotation
matrix R and translation vector t that together minimize the expression,
1 N
FRE 2 = ∑ R ( xi + Δxi ) + t − ( yi + Δyi ) ,
2
(3)
N i =1

where xi and yi are 3-by-1 vectors representing corresponding points in two spaces for which at least three of the xi
are not collinear, and Δxi and Δyi are 3-by-1 vectors representing localization errors in the two spaces. The rotation
matrix is restricted to be orthogonal, which means that R t R = I , where I is the 3-by-3 identity matrix. The points yi
arise from an initial misregistration caused by a rotation R ( ) and translation t ( ) , of the xi ,
0 0

yi = R ( ) xi + t ( ) .
0 0
(4)

We model the Δxi and Δyi as random, independent vectors of FLE, whose elements are statistically independent and
drawn from a normal distribution with zero means and variances σ 12 = FLE12 3 and σ 22 = FLE 22 3 , respectively. Thus,
the localization errors in the two spaces are isotropic. We can take advantage of the isotropy of FLE1 by noting that it
results in both Δxi and RΔxi having the same distribution. This observation allows us to rewrite Eq. (3) as
N
1
∑ Rx
2
FRE 2 = i + t − yi − Δξ i , (5)
N i =1

where Δξi = Δyi − RΔxi , is the “two-space” localization error vector for point-pair i, and its elements are independent
and normally distributed with zero means and variance σ 2 = σ 12 + σ 22 . We define FLE = FLE12 + FLE 22 = 3σ to be
2
the “two-space” FLE. Once the rotation and translation have been found that minimize FRE , they can be used to
determine the vector TRE of target registration error at any point x that is not used as a fiducial point:

(
TRE ( x ) = Rx + t − R ( ) x + t (
0 0)
). (6)
2.2. Linearization
In 1979, Sibson showed how derivations of error statistics for this problem could be made tractable by (a) assuming that
FLE is small, (b) approximating to first-order in FLE, (c) moving the origin of the coordinate system to the centroid of
the xi , (d) reorienting the coordinate system along the principal axes of the xi , and (e) separating the rotational and
translational problems [2]. He used this approach to investigate FRE; we and others have used it to investigate TRE [4],
[5], [7], [8]] and FRE [3]. For our present investigation, we have developed a new approach. We employ (a) and (b), but

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 we omit (c), (d), and (e). Thus, we solve to first order in FLE, but we retain the laboratory coordinate system, and we
solve for both the rotation and the translation simultaneously. Solving the first-order problem allows us to cast the
problem as a simple unconstrained set of 3N linear algebraic equations in six unknowns of the form: Cq = e , where C
is a 3N-by-6 matrix, e is a 3N-by-1 vector, and q , the unknown, is a six-element column vector.

We begin by defining xi( 0) = R (0 ) xi , and Δt = t − t ( ) , which allows us to transform the vector whose squared length
0

appears in the summation in Eq. (3) as follows:

( 0
t
)
R ( xi + Δxi ) + t − ( yi + Δyi ) = R R ( ) R ( ) xi + RΔxi + t − R ( ) xi − t ( ) − Δyi = RR ( ) − I R ( ) xi + t − t (
0 0 0
( 0
t
) 0
( 0)
) − Δξ i
(7)
( − I)x
t (0)
+ Δt − Δξi = ΔRxi( ) + Δt − Δξi ,
0
= RR ( ) 0
i

t
where we have used Eq. (4) and have defined ΔR = RR ( ) − I . Using Eq. (7) in Eq. (3) gives us 0

N
1 2
FRE 2 =
N
∑ ΔRx ( ) + Δt − Δξ
i =1
i
0
i . (8)

From assumption (a), we know that the components of Δξi will be small. If they were all zero, then Eq. (8) tells us that
we could achieve a perfect minimum of zero for Eq. (3) by setting ΔR and Δt to zero. For finite but small Δξi , we see
from this same equation that, when FRE is minimized, the elements of both ΔR and Δt will be small. We note that the
elements of ΔR t ΔR can be expected to be small relative to those of ΔR , because they are of second degree in the
elements of ΔR . Following Sibson, we now make the assumption that the Δξi are small enough to render the elements
of ΔR t ΔR negligible in comparison to the elements of ΔR . We note that

( ) ( RR )
t t t
ΔR t ΔR = RR ( ) − I 0 (0)
−I
( 0 )t
= I − R ( ) R t − RR
0
+I (9)
= − ( ΔR + ΔR ) , t

where we have used the orthogonality of rotation matrices to go from the first line to the second. From Eq. (9), we see
that, if the elements of ΔR t ΔR are indeed negligible in comparison to the elements of ΔR , then ΔR t + ΔR ≈ 0 , which
means that ΔR is antisymmetric, i.e., ΔR t = −ΔR .

Thus, we see that, for small FLE, the non-linear restriction R t R = I , is replaced by the linear restriction that
ΔR t = −ΔR . This relaxed constraint is essential to the original approach of Sibson on the statistics of FRE [1], the
approaches of the subsequent work on the statistics of TRE [3], [5], [7], and our current approach. However, we show in
simulations below that our results hold to an excellent approximation even without linearization. The difference being
that we can prove that it holds for all configurations and all values of FLE for the linearized equations, whereas for the
nonlinear version, we can show it only for those cases that are simulated. Using our definition of ΔR in Eq. (6) gives
( 0
t
TRE ( x ) = RR ( ) − I R ( ) x + t − t ( ) = ΔRx ( ) + Δt , ) 0 0 0
(10)

where we have defined x ( 0 ) = R (0 ) x and have used Δt = t − t ( ) .

0

2.3. Some useful linear-algebra results

The minimization of Eq. (8), subject to ΔR t = −ΔR is equivalent to finding the least-squares solution to an over-
determined set of 3N equations,

( ΔRx ( ) ) i
0
j
+ Δt j = Δξi j , i = 1, 2,... N , j = 1, 2,3 , (11)

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 where the subscript j enumerates the components of three-dimensional vectors. By defining the 3N-by-6 matrix C,

⎡ X 1( 0) I ⎤
⎡ 0 xi(3 ) − xi(2 ) ⎤
0 0
⎢ ( 0) ⎥
⎢X2 I⎥ ⎢ 0 ⎥
where X i(
0)
= ⎢ − xi(3 ) xi(1 ) ⎥ , and xik( ) = kth component of xi( ) ,
0 0 0
C=⎢ ⎥, 0 (12)
⎢ ... ... ⎥ ⎢ (0) (0) ⎥
⎢⎣ xi 2 − xi1 0 ⎥⎦
⎢ X ( 0) I ⎥
⎣ N ⎦

and defining the 3N-by-1 vector e with elements e3(i −1)+ j = Δξij , i = 1,...,3N , j = 1, 2, 3 , we can transform Eqs. (11) into

Cq = e , (13)

where q is column vector with elements ΔR32 , ΔR13 , ΔR21 , Δt1 , Δt2 , Δt3 . With Eq. (13), we have transformed the problem
into a generic linear-algebra problem, and we need to establish some properties of the least-squares solution to that
problem. The least-squares solution of Eq. (13) can be effected by means of the pseudo-inverse,
qmin = C *e , (14)
where C * = ( C t C ) C t , is the pseudo-inverse of C. The elements of the 3N-by-1 vector
−1

f min = e − Cqmin , (15)

1
which are the residual errors in the solution. Eq. (15) can be rewritten as follows,
f min = Ae , (16)
where A = I ( 3N ) − B , I ( M ) is the M-by-M identity matrix, and the 3N-by-3N matrix B is equal to C *C , which equals
C ( C t C ) C t . B is symmetric, and it can be seen, as follows, that B is also idempotent:
−1

( )
B 2 = C ( C t C ) C t C ( C t C ) C t = C ( C t C ) C t C ( C t C ) C t = C ( C t C ) C t = B.
−1 −1 −1 −1 −1
(17)

Because B is symmetric, its eigen decomposition yields B = VB Λ BVBt , where Λ B and VB are real and VB is orthogonal.
Using this decomposition we find that B 2 = (VB Λ BVBt )(VB Λ BVBt ) = VB Λ B (VBtVB ) Λ BVBt = VB Λ 2BVBt , and substituting these
expressions for B and B 2 in Eq. (17) gives
VB Λ 2BVBt = VB Λ BVBt . (18)

Multiplying both sides of Eq. (18) on the left by VBt and on the right by VB , we have Λ 2B = Λ B , or equivalently that
Λ 2Bii = Λ Bii . Thus the 3N diagonal elements of Λ B are each equal to 1 or 0 (a well established property of idempotent
matrices). By inspecting the trace of B we can determine how many of these elements are equal to 1:
( )
trace ( B ) = trace C ( C t C ) C t = trace C t C ( C t C )
−1
( −1
) = trace ( I (6)) = 6, (19)

where in the second step, we have used the property that trace ( AB ) = trace ( BA) . We note also that
3N
trace ( B ) = trace (VB Λ BVBt ) = trace (VBtVB Λ B ) = trace ( Λ B ) = ∑ Λ Bii . (20)
i =1

Since each term in the sum in Eq. (20) is equal to 1 or 0, we see that exactly six of the 3N diagonal elements of Λ B are
equal to 1, with 3N-6 being equal to zero. For convenience, we now, without loss of generality, permute the columns of

1
The quantity symbolized by f in Eq. (15) is unrelated to the quantity symbolized by f in Eq. (2).

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 VB and the rows and columns of Λ B so that the first 3N − 6 diagonal elements of Λ B are equal to zero and the last six
are equal to 1. Turning now to the matrix A, we see that

A = I ( 3N ) − B = I ( 3N ) − VB Λ BVBt = VB ( I ( 3N ) − Λ B )VBt = VB Λ AVBt , (21)

where Λ A is a 3N-by-3N diagonal matrix equal to I ( 3N ) − Λ B . Because the first 3N − 6 diagonal elements of Λ B are
equal to zero, we see that the first 3N − 6 diagonal elements of Λ A are equal to 1; and because the last six diagonal
elements of Λ B are equal to 1, we see that the last six diagonal elements of Λ A are equal to 0.

Using this result in our expression for the vector f min of residual errors, we have f min = Ae = VB Λ AVBt e = VB Λ Ae% , where

e% = V t e (22)
Thus,
3N 3 N −6 3N 3 N −6
( f min )k = ∑ (VB )kj ( Λ A ) jj e% j = ∑ (VB )kj ⋅1 ⋅e% j + ∑ (VB )kj ⋅ 0 ⋅e% j = ∑ (VB )kj e% j , (23)
j =1 j =1 j =3 N −5 j =1

from which we see that each element of f min is a function of only the first 3N − 6 elements of e% .

2.4. FRE in terms of FLE

We now return to the registration problem. We note that the elements of f min in Eq. (23) are the components of the
individual fiducial registration error vectors, FREi , of those points. Specifically, ( f min )3(i −1)+ j = FREij ,
i = 1,...,3N , j = 1, 2, 3 . We recall also that the elements of e in Eq. (22) are the components of the fiducial localization
error vectors, FLE, of the N fiducial points, Therefore, each component of FREi for each fiducial point is a function of
only the first 3N − 6 elements of e% , which are, by Eq. (22), linear combinations of the components of the FLE of the
individual fiducial points.

2.5. TRE in terms of FLE

Our expression for TRE ( x ) in Eq. (10) can readily be transformed into a simple matrix-times-vector multiplication,
δ = Dq , (24)
by defining δ j = TRE ( x ) j , j = 1, 2, 3 and defining the 3-by-6 matrix,

x3(
0)
⎡ 0 − x2( ) 0 ⎤
0
1 0
⎢ 0 ⎥
D = ⎢ − x3( ) x1(
0)
xk( ) = kth component of point x ( ) .
0 0
0 0 1 0 ⎥, (25)
⎢ (0) ( 0) ⎥
⎣⎢ x2 − x1 0 0 0 1 ⎦⎥

For the optimal transformation, the expression for TRE ( x ) becomes,

δ min = Dqmin . (26)

A crucial step in our derivation is to prove that there exists a 3-by-3N matrix G such that D = GC. Our proof begins by
considering the singular-value decomposition of C, U ΛV t = C , where U is a 3N-by-3N orthogonal matrix, Λ is a 3N-
by-6 matrix for which Λ ij is zero for i ≠ j , the six diagonal elements Λ ii are the singular values of C, and V is a 6-by-6
orthogonal matrix. Our proof requires that the six singular values Λ ii of C all be nonzero. This requirement is equivalent
to the requirement that the columns of C be independent. We prove that they are independent via proof by contradiction.
Thus, we assume instead that the columns of C are linearly dependent, which means that for some set of six constants,

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 ∑
6
a1 , a2 ,..., a6 , i =1
ai Ci = 0 , where each Ci is a column of C. Because each column is of length 3N, this constraint is
equivalent to 3N equations, which have the form

xi(2 ) a3 − xi(3 ) a2 = a4 ⎫
0 0

⎪⎪
xi(3 ) a1 − xi(1 ) a3 = a5 ⎬ for i = 1, 2,..., N .
0 0
(27)
⎪
xi(1 ) a2 − xi(2 ) a1 = a6 ⎪⎭
0 0

These 3N equations are in turn equivalent to the N cross products: xi( ) × ( a1 , a2 , a3 ) = ( a4 , a5 , a6 ) . In order for all N of
0

these cross products to be equal to the same constant vector, all N points xi( ) must be collinear. We note from Section
0

2.1 above that at least three of the points xi must not be collinear, and we note also that rotating and translating these
points to produce the points xi( ) does not change the linearity of points. Thus, our assumption that the columns of C are
0

dependent has led to a contradiction. Therefore, the columns of C are in fact independent, and therefore the singular
values of C are all nonzero.

To construct the required matrix G, we first define a 3-by-6 matrix D̂ =DV, where V is the right-hand orthogonal matrix
from the singular-value decomposition of C above. Then, we define the 3-by-3N matrix Ĝ , whose elements are

⎧⎪ Dˆ Λ jj , for j = 1, 2,...,6 ⎫
Gˆ ij = ⎨ ij ⎬ , i = 1, 2,3 , (28)
⎩⎪ 0 , for j = 7,8,...3N ⎭
where the Λ jj are the singular values of C. Our proof that they are nonzero justifies the division on the first line. From
this definition for Ĝ , we see that, for i = 1,2,3 and j = 1,2, …, 6,
6 3N
Dˆ ij = Gˆ ij Λ jj = ∑ Gˆ ik Λ kj = ∑ Gˆ ik Λ kj , (29)
k =1 k =1

where we have used the fact that Gˆ ik Λ kj = 0 for k > 6 when we extended the summation limit from 6 to 3N. From Eq.
(29) we have that D̂ = Gˆ Λ . Multiplying both sides of this equation on the right by V t gives D = Gˆ ΛV t . Finally, we
define G = GU ˆ t . From this definition, we see that D = GU ΛV t = GC. Thus, we have shown that for the point
registration problem there always exists a matrix G such that D = GC.

Using G, the least-squares solution of Eq. (13), as given by Eq. (14), the definition of the matrix B, and the eigen
decomposition of B in Eq. (26) gives

δ min = GCqmin = GCC *e = GBe = GVB Λ BVBt e = GVB Λ B e% . (30)

Thus,
3N 3 N −6 3N 3N
(δ min )k = ∑ ( GVB )kj ( Λ B ) jj e% j = ∑ ( GVB )kj ⋅ 0 ⋅e% j + ∑ ( GVB )kj ⋅1 ⋅e% j = ∑ ( GVB )kj e% j , (31)
j =1 j =1 j = 3 N −5 j = 3 N −5

from which we see that each component of TRE ( x ) is a function of only the last 6 elements of e% , which are, by Eq.
(22), linear combinations of the components of the FLE of the fiducial points.

2.6. Independence of FRE and TRE

In the point-registration problem (Section 2.1), the components of FLE of the N points are statistically independent, and
hence are uncorrelated, with zero means and variances equal to σ 2 . In the Appendix we show that, if the elements of e,
which comprise these FLE components, have these properties, then the elements of e% are also uncorrelated with zero
mean and variance σ 2 . In Section 2.4, we found that each component of FRE for each fiducial point, which is also an

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 element of f min , is a function of only the first 3N − 6 elements of e% , while in Section 2.5 we found that each component
of TRE ( x ) , which is also a component of δ min , is a function of only the last 6 elements of e% . Since the elements of e%
are uncorrelated, the components of FRE of the N points and the components of TRE ( x ) are also uncorrelated.
Furthermore, in the point-registration problem, the components of FLE are also normally distributed, and we show also
in the Appendix that, as a result, the elements of e% are not only uncorrelated but are also statistically independent.
Therefore, the components of FRE of the N points are not only uncorrelated with the components of TRE ( x ) but also
independent of them. This independence means that there is no measure based on the goodness of fit of the fiducials
resulting from a given registration that gives any information whatever about TRE ( x ) for that registration.

Finally, we note that the overall fiducial registration error FRE from Eq. (3) is given in the linearized problem by Eq. (8)
and can be expressed in terms of f min as FRE = t
f min f min N and that the length of the vector TRE ( x ) can be
expressed in terms of δ min as TRE ( x ) = δ min
t
δ min . Since the elements of f min are statistically independent of those of
δ min , any function of only f min is independent of any function of only δ min . As primary examples, FRE is statistically
independent of TRE ( x ) . Thus it is wrong to use fluctuations in a system’s FRE as indicators of fluctuations in
registration accuracy. Since they are independent, FRE and TRE are also uncorrelated, i.e., FRE⋅ TRE = 0. We let
CC ( FRE, TRE ) be the correlation coefficient of FRE and TRE ( x ) ,

CC ( FRE,TRE ) = ( FRE − μFRE )( TRE− μTRE ) (σ FREσ TRE ) , (32)

where we have abbreviated TRE ( x ) as TRE, and are letting μ and σ indicate means and standard deviations.
Because FRE and TRE are linear in FLE, and μFLE = 0, both μFLE and μFLE are also zero. Thus, we have shown that,
to first order in FLE, CC ( FRE, TRE ) = 0, meaning that there is no correlation between FRE and TRE.

3. SIMULATIONS
Our proof relies on linearization via a first-order approximation, but previous work [1]-[8] has shown that this
approximation is extremely accurate for practical fiducial and target arrangements, for which FLE is typically on the
order of a few percent or less of the separation between fiducials. Nevertheless, we also present statistics obtained from
simulations that show that our conclusion is valid for the exact problem as well as the linearized one. We implemented
simulations using Matlab (Version 7.6.0.324/R2008a, The Mathworks, Natick, MA). For each simulation experiment,
we specified a set of N fiducial positions xi , a target position x, in the first space and a value for FLE. We then applied a
rotation R ( ) and translation t ( ) to produce N corresponding unperturbed positions yi(
0 0 0)
in the second space as
prescribed by Eq.(4). Then, we repeated the following three steps 100,000 times:
(1) Perturb the fiducial positions in the second space with 3N components, Δξij , of fiducial localization error drawn
from a random distribution with zero mean and variance of FLE/3, to produce N perturbed positions yi (Eq. (5)).
(2) Find R and t that minimize the exact registration formula of Eq. (3) (using the method of singular-value
decomposition [Algorithm 8.1 of reference [13]).
(3) Calculate both FRE and TRE ( x ) .

After completion of these repetitions, we estimate the correlation coefficient CC ( FRE, TRE ) of Eq. (32) from the
sample of 100,000 measurements (using the function corrcoef in Matlab). If our theory is correct, then for small FLE the
difference between our estimation of CC and zero will be insignificant. To test our theory, we performed four
experiments.

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 ITRE(x)I versus FOE
Experiment 1. Deep-brain stimulation surgery. We placed four fiducials
at positions that were measured in a patient CT image (after IRB permission
was obtained) of the centroids of anchors implanted in the calvarium to 2

support fixtures used to guide the placement of stimulator leads during

surgery for deep-brain stimulation (DBS). These anchors serve as fiducials to
guide lead placement in the deep-brain region [12], so we selected a target 1 .5

position x near the center of this region. The specific positions used were as uJ

follows (in mm): H

⎡197 ⎤ ⎡109 ⎤ ⎡ 83⎤ ⎡ 202 ⎤ ⎡144 ⎤

x1 = ⎢⎢217⎥⎥ , x1 = ⎢⎢225⎥⎥ , x1 = ⎢139 ⎥ , x1 = ⎢⎢132 ⎥⎥ , x = ⎢⎢155⎥⎥ .
⎢⎣115 ⎥⎦ ⎢⎣121⎥⎦ ⎢⎣127 ⎥⎦ ⎢⎣130 ⎥⎦ ⎢⎣ 57 ⎥⎦ 05

For R ( ) , we used a rotation of 10, 20, and −30 degrees about the x, y, and z
0

axes, and we chose t ( ) equal to (7, −10 , 100) mm (an arbitrary

0
0 0.5 1 1.5 2
FOE
misregistration). We set FLE to 1 mm, which is a realizable value and is
small compared to the spread of fiducials: The root-mean-square distance of Figure 2. Experiment 1: Scatter plot of
the fiducials from their mutual centroid is 68 mm. In Figure 2, we show a |TRE(x)| versus FRE. For clarity, just
scatter plot of TRE ( p ) versus FRE from this simulation. For clarity, only 1% of the 100,000 registrations are
plotted. The dashed lines show average
1% of the points are plotted. The resulting correlation coefficient CC = values. The correlation coefficient, CC is
0.00446. only 0.00446. (Experiment 2 shows that
CC is in fact statistically insignificant.)
Experiment 2. Deep-brain stimulation surgery. The magnitude of CC in
Experiment 1 is small, but to determine whether its difference from zero is
significant, we repeated the experiment 30 times. We observed a mean CC of
5.2 ×10−5 ± 3.9 ×10−3 , and Matlab’s ttest yields a 95% confidence interval
of ± 1.4 ×10−3 with p = 0.94. Thus, at p < 0.05, the correlation between FRE
and TRE is insignificant, which supports our claim that it is zero for small
FLE.
Experiment 3. Random fiducials and targets. To test our theory on a range
of fiducial configurations and target positions, we performed an experiment
similar to that of previous publications [3]-[8], in which points are randomly
chosen from within specified boundaries with random misregistrations. We
tested four sets of fiducials, with 3, 10, 20, and 50 fiducials, respectively,
chosen randomly from within a cube with side = 200 mm with a target
chosen randomly for each set from within a cube of side 400 mm, employing
random misregistration by rotating about x, y, and z by angles normally
distributed with mean zero and a standard deviation of 90 degrees and
translating with components along x, y, and z normally distributed with mean
Figure 3. Experiment 4: Effect on CC of
zero and a standard deviation of 100 mm. For each configuration we ran 30 increasing FLE. The configuration used in
experiments with FLE = 1 mm and found that deviations of the mean of CC Figure 2 is reused, but FLE is varied from
from zero were insignificant at p < 0.05 for all four sets (all p > 0.59 for all 1 to 70 mm. The solid line is the mean
four), supporting our claim that, for small FLE, FRE and TRE are value over 30 runs, the 95% confidence
uncorrelated. limits are shown with dashed lines. The
difference from zero is insignificant for
Experiment 4. Effect of large FLE. Our theory is based on a linearized FLE ≤ 10 mm (p < 0.05), and CC is less
form of the registration problem, which is appropriate only for small FLE. To than 0.03 over the entire range.
determine the effect on CC of the size of FLE, we repeated the DBS problem
of Experiment 2 for values of FLE ranging from 1 mm to 70 mm. (This study
involves 12 x 30 x 100,000 = 36 million registrations.) Figure 3 shows the
results. The difference of CC from zero is insignificant (p < 0.05) for FLE ≤
10 mm, which supports our claim for small FLE, and for larger values of
FLE, CC is less than 0.03.

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 All four of our experiments support our conclusion that there is no correlation between FRE and TRE in rigid, point
registration for small FLE and that, even for large FLE, the correlation is negligible.

4. DISCUSSION
It has been common practice for many years for surgeons who employ systems for image guidance during a procedure to
assume that the value of fiducial registration error (FRE) measured for that procedure, or some other estimate of
registration accuracy based on goodness of fiducial fit, can be used as an indicator of the expected level of accuracy for
the patient on whom they are about to operate. This paper presents the first demonstration that this assumption is wrong.
While there are reliable estimates available for the expected FRE and target registration error (TRE) for a given level of
fiducial localization error (FLE), such as those given in Eqs. (1) and (2), we have demonstrated in the current work that
there is no relationship between variations of FRE and TRE about these expected values. Their variations are
uncorrelated. In fact they are to first order completely independent of one another. Our demonstration is based both on a
proof and on numerical simulations. Our proof is based on a novel method for analyzing the statistics of error in rigid-
body point registration that avoids some of the complexity heretofore associated with the statistical analysis of error in
this problem, thereby rendering the solution more tractable. In particular, we avoid the separation of the problem into the
rotation problem and the translation problem and reduce it to a basic linear algebra property, which is related to the
orthogonality principle of linear systems [14]. In our theoretical work we analyze only the linearized problem, which is
accurate only for small FLE. However, our simulations indicate that our conclusions hold for the exact problem as well.
In our experiments we show that FRE and TRE are merely uncorrelated, but in our theoretical derivations, we have
shown that to first order all components of TRE ( x ) at any point x are completely independent of all components of the
individual fiducial registration errors FREi for all N fiducials. Thus there is no measure based on the goodness of fit of
the fiducials that gives any information whatever about TRE ( x ) . This result does not detract from the importance of
Eqs. (1) and (2), which relate mean values. Eqs. (1) can be used to estimate the FLE distribution from measurements of
FRE for many cases. Based on this estimate, Eq. (2) can then be used to estimate TRE for a given case according to the
fiducial configuration and target position for that case, but the FRE for a given case plays no role in the estimate of TRE
for that case.

When an image-guidance system displays some estimate of registration accuracy based on the goodness of fit of the
fiducials, it is natural for the surgeon using it to assume that the manufacturer or some regulatory agency has verified
that a better fit implies a better accuracy. If our results are correct, however, then it is clear that such a verification has
never been done, because it is impossible to do. Thus, any information provided by a navigation system that purports to
infer accuracy on the basis of the fiducial fit must be fallacious and should be ignored.

What, then, is the purpose of displaying a measure based on the goodness-of-fit? In particular, is there any worthwhile
information can be gained for a given case from the measurement of FRE for that case? Yes. A larger than normal FRE
for a given case indicates a larger than normal probability that the registration system has been compromised for this
case. Such a probability can be formalized [3] to support a decision that the system is either working properly or is not.
(A likely reason that a system is not working properly is that some localizations were done incorrectly or that the
fiducials have moved relative to the anatomy during the patient’s trip from the scanner to the operating room.) Thus, if
the surgeon sees a measure that is smaller than usual, or not much larger than usual, it is a good sign that there are no
problems with the system and that therefore Eq. (2) can be used to predict registration accuracy (based on an estimate of
FLE gleaned from previous measurements of FRE). If a very large measure is displayed, however, the fiducials should
be re-localized in physical space and/or image space. If the measure remains very large, then it is likely that the system
has been compromised and should not be used for the current case. Our current results have no bearing on that decision.
However, if the system is working properly, we conclude that the value of FRE gives no additional information whatever
about actual registration accuracy for a given case on a given day.

5. CONCLUSION
There is no correlation between FRE and TRE for point registration. In fact, we have shown that it is impossible to
predict variation in TRE based on the variation of any measure of goodness of fiducial fit. We have shown it by (a)
presenting a proof that to first order there is no relationship whatever between fluctuations in the fit measured for a given

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 case and the accuracy of image guidance for that case and (b) showing via numerical simulation that there is no
correlation between FRE and TRE for the exact problem as well. Thus, surgeons should stop using the value of FRE, or
any indication of accuracy based on goodness of fiducial fit, that is displayed by their image-guidance system as an
indication of the expected level of accuracy for the patient on whom they are about to operate. FRE is a reasonable
indicator of whether or not the system is functioning properly for a given procedure on a given patient, but, if the system
is functioning properly, then no measure of the goodness of fiducial fit provides any information about the level of
accuracy achieved by the system for that patient.

6. APPENDIX
In this appendix we consider some statistical effects of a linear operation on a M-by-1 vector e to produce a vector e% :

M
e%i = ∑Vki ek (33)
k =1

All these are known results, but we include these derivations here for completeness.

6.1 If the mean of e is zero, then the mean of e% is zero.

That the mean is zero is easily seen by computing the expectation value, which we denote by . , of both sides of Eq.
(33):
M M M
e%i = ∑V
k =1
e
ki k = ∑Vki ek = ∑Vki ⋅ 0 = 0
k =1 k =1
(34)

6.2 If the elements of e are uncorrelated with equal variances and V is orthogonal, then the elements e% are
uncorrelated.

Because of Eq. (34), the correlation of e%i and e% j is equal to ( e% −

i e%i ) ( e% j − e% j ) :

) ( e% )
M M M M
( e% −
i e%i j − e% j = ∑Vki ( ek − ek ) ∑V ( e lj l − el ) = ∑∑VkiVlj (ek − ek )( e l − el )
k l k l
(35)
M M M
=σ 2
∑∑V V δ
k l
ki lj kl =σ 2
∑V V k
ki kj = σ δ ij ,2

where we used the fact that the elements of e are uncorrelated and equal in going from the first line to the second, have
defined σ 2 = ei2 to be the variance of an element of e, and used the orthogonality of V in the last step.

6.3 If the elements of e are independent and normally distributed with equal variances and V is orthogonal, then
the elements of e% are independent and are normally distributed.

We note that, since the elements ei are independent and normally distributed, their joint probability density has the form

⎛ −1
( ) ( ) ( ) ⎞
M M
exp −ei 2 / ( 2σ 2 ) = σ 2π
−1 −M
p1,2,..., M ( e1 , e2 ,..., eN ) = ∏ σ 2π exp ⎜ 2 ∑e 2
⎟, (36)
⎝ 2σ
i
i =1 i =1 ⎠

where we have used the fact that the means of the ei are zero.2 Because each e%i is a linear combination of the ei , their
joint density has the form (by generalizing the derivations on pages 199-201 of [14] from two variables to M variables),

2
Zero means are not necessary for this derivation. They simply reduce its complexity. Since the means are in fact zero, we take
advantage of that fact to simplify the equations.

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 q1,2,..., M ( e%1 , e%2 ,...e%M ) = J p1,2,..., M ( z1 , z2 ,..., zM ) ,
−1
(37)

where J = det (V t ) and z = (V t ) e% . Since V is orthogonal, J = 1 and (V t )

−1 −1
= V. Using these properties and Eq. (36)
in Eq. (37) gives us that

( ) ⎛ M
( 2σ ) ⎞⎟ = (σ ) ( )
−M −M
q1,2,..., M ( e%1 , e%2 ,...e%M ) = σ 2π exp ⎜ − ∑ (Ve% )i exp − (Ve% ) Ve% 2σ 2
2 t
2
2π
⎝ i =1 ⎠

( ) exp ( − e% tV tVe% 2σ 2 )
−M
= σ 2π (38)
⎛ M ⎞
= (σ 2π ) exp ( − e% t e% 2σ 2 ) = σ 2π ( )
−M −M
exp ⎜ − ∑ e%i 2 2σ 2 ⎟ ,
⎝ =1i ⎠

where we have used the orthogonality of V in going from the second line of Eq. (38) to the third line.

M
Eq. (38) can be written as a product of functions of the individual e%i as follows: q1,2,..., M ( e%1 , e%2 ,...e%M ) = ∏ qi ( e%i ), where
i =1

( ) ( ( 2σ ) ) ,
−1
qi ( e%i ) = σ 2π exp −e%i 2 2
(39)

which is of normal form. Since the joint probability density of the e%i is equal to the product of individual functions, the
e%i are mutually independent. Since the individual functions are of normal form, they are normally distributed.

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