POLITECNICO DI MILANO Generation of a patient specific predictor for osteoporotic risk of fracture

132 Pages·2013·10.64 MB·English

POLITECNICO DI MILANO
Facoltá di ingegneria dei sistemi
Corso di Laurea Specialistica in Ingegneria Biomedica
Generation of a patient specific predictor for
osteoporotic risk of fracture of the femoral neck
Relatore:
Tomaso Villa Maria Tobia
Correlatore:
Marco Viceconti
Relazione della prova finale di:
Anna Caimi 770324
Gloria Casaroli 765186
Anno Accademico 2011/2012

Ringraziamenti
Desideriamo porgere il primo sentito ringraziamento al Prof. Marco Viceconti per
l’estrema disponibilitá e cortesia dimostrateci in questi mesi, per le grandi opportunitá
che ci ha offerto, per la realtá che ci ha fatto conoscere e nella quale ci ha introdotto;
un forte ringraziamento va al Prof. Tomaso Villa, che ci ha offerto la possibilitá di
compiere un’esperienza di tesi all’estero che è stata la migliore della nostra carriera,
sostenuto durante tutto il suo corso e ci ha sempre mostrato grande disponibilitá. Un
ringraziamento speciale va a Giovanna Farinella, che ci ha seguito passo a passo nello
svolgimento del nostro lavoro, fornendoci sempre grande aiuto e competenza, oltre che
aver stretto con noi un forte legame di amicizia.
Un grazie particolare va a tutti coloro che hanno condiviso con noi l’esperienza
a Sheffield rendendola davvero speciale, e in particolare alle nostre colleghe Sandra e
Francesca che sono state due perfette compagne d’avventura.
Grazie anche a tutti i nostri compagni di corso per gli anni di studio, per i progetti
di gruppo, per le risate e per tutti i momenti belli passati qui al Politecnico e durante
la vita normale di tutti i giorni.
Grazie anche a tutti gli amici di sempre ed alle persone noi care, per le serate, i
week-end, per averci parlato di tutto fuorché dello studio, per averci capito, distratto
e consolato con la loro simpatia e il loro affetto; in particolare grazie a Massimo e a
Riccardo, che ci sono stati accanto piú di ogni altro e ci hanno sostenuto nonostante
la grande distanza.
Un ringraziamento particolare va infine alle nostre famiglie, per averci incoraggiato
nelle scelte, sostenuto nei 5 anni, aver condiviso con noi i momenti di soddisfazione
e consolato in quelli piú difficili e per averci regalato la possibilitá di compiere questa
esperienza all’estero. Grazie, senza di voi, per noi, oggi sarebbe un giorno qualunque.
Anna e Gloria
iii

Contents
Contents v
List of Figures vii
List of Tables xi
Abstract xiii
Sommario xix
1 Introduction 1
1.1 Osteoporosis: social and economic burden . . . . . . . . . . . . . . . . . 1
1.2 The Clinical State of the Art . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 The VPHOP project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4 The aim of our work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2 Anatomy and Mechanics 13
2.1 Body’s reference system and planes . . . . . . . . . . . . . . . . . . . . . 13
2.2 Relative position . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.3 Musculoskeletal anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2.3.1 Anatomy and physiology of bone . . . . . . . . . . . . . . . . . . 15
2.3.2 The pelvis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.3.3 The femur . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3.4 The hip joint and angle . . . . . . . . . . . . . . . . . . . . . . . 22
2.4 Bone tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.4.1 Composition of bone . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.4.2 Bone Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
v
vi CONTENTS
2.4.3 Bone mechanobiology . . . . . . . . . . . . . . . . . . . . . . . . 29
2.4.4 Effects of underloading and overloading . . . . . . . . . . . . . . 31
2.5 Hip Biomechanics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.5.1 Hip muscles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.5.2 Hip kinematic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.6 Definition and basic information . . . . . . . . . . . . . . . . . . . . . . 35
2.6.1 The importance of Gait analysis for this study . . . . . . . . . . 37
2.6.2 Effect of sub-optimal neuromotor control . . . . . . . . . . . . . 41
2.6.3 Hypothesis of our model . . . . . . . . . . . . . . . . . . . . . . . 43
3 Material and methods 45
3.1 Patients’ cohort and CT scanning . . . . . . . . . . . . . . . . . . . . . . 45
3.2 Materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
3.2.1 Segmentation and morphing . . . . . . . . . . . . . . . . . . . . . 48
3.2.2 BoneMat software . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.2.3 Structure of msf file . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.3 The mechanical load scenarios . . . . . . . . . . . . . . . . . . . . . . . . 64
3.3.1 Strength loading scenario . . . . . . . . . . . . . . . . . . . . . . 64
3.3.2 Femur-fall Charité database . . . . . . . . . . . . . . . . . . . . . 68
4 Results 71
5 Conclusion 87
6 Future development 91
Appendix 93
Descriptive statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
The Mann-Whitney test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
ROC curve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Logistic regression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Bibliography 107
List of Figures
1.1 Image of the DXA of a femur. . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 FRAX interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 The graph shows fracture rates per 100 person-years by phenotypic and T-
scoreaccordingtotheNationalOsteoporosisRiskAssessmentStudy. Across
all phenotypic groups, low BMD is a consistent risk factor for fracture. . . . 6
1.4 Image representation of the VPHOP project. . . . . . . . . . . . . . . . . . 7
1.5 Biomed Town interface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.6 Physiomspace interface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.7 OpenClinica interface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.8 VOP Hypermodel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.1 Body planes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2.2 Structure of long bone: external structure, epiphysis and diaphysis and a
section of bone with a view of internal structure and component. . . . . . . 16
2.3 Distribution of compact and cancellous bone in the upper part of the femur. 17
2.4 Structureofthecancellousandcorticalbone: arepresentationoftrabeculae
and of osteons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.5 Maximum strength with minimum weight. . . . . . . . . . . . . . . . . . . . 20
2.6 Structure of the pelvis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.7 Arepresentationofforcesthatactonthepelvisfromfemurandfrompelvis
to femur. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.8 Anterior and posterior view of the femur. . . . . . . . . . . . . . . . . . . . 22
2.9 The coxofemoral joint. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.10 CCD-angle in three configuration: coxa norma, coxa vara and coxa valga. . 25
vii
viii List of Figures
2.11 Lightmicrographofosteoclasts(arrows). Typicalmultinucleatedosteoclast
nestled in its Howship’s lacuna. Bone (B), calcified cartilage (CC). Decal-
cified, methylene blue, and azure II stained section; original magnitude X
800. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.12 Light micrograph of osteoblasts. Spicule of calcified core line with os-
teoblasts (Ob) and thin osteoid (arrows). Osteoprogenitor cells (Opc) are
located between osteoblasts and blood vessel. Original magnification X600. 28
2.13 Diagrammatic representation of working hypothesis of bone resorption. A
typical resting bone surface is lined by a thin demineralized layer (OO), a
lamina lamitans (LL), and a flat bone-lining cells (BLC). . . . . . . . . . . 30
2.14 Hip joint lateral view. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
2.15 Representation of the main hip muscles. . . . . . . . . . . . . . . . . . . . . 34
2.16 Principal movements’ angles . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.17 Representationofanatomicalsegmentsofhumanbodyandglobalandlocal
coordinate systems.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.18 Coordinate system for measured hip contact forces. The hip contact force
vector –F and its components –F , (cid:0)F , (cid:0)F acts from the pelvis to the
x y z
implant head and is measured in the femur coordinate system x;y;z. . . . . 38
2.19 Joint centres, reference points and coordinate system for gait analysis. . . . 39
2.20 ContactforceFoftypicalpatientNPAduringnineactivities. Contactforce
F and its components –F , (cid:0)F , (cid:0)F . F and –F are nearly identical. . . . 40
x y z z
2.21 Contact force vector F of typical patient NPA during nine activities. The
z-scales go up to 300% BW. Upper diagrams: Force vector F and direction
Ay of F in the frontal plane. Lower diagrams: Force vector F and direction
Az of F in the transverse plane. . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.22 Comparison of the predicted pattern of the hip load (solid black line) with
thevariabilityofthehiploadmagnitude(greyband)measuredon4subjects
through an hip prosthesis instrumented with a telemetric force sensor. . . . 42
3.1 Phantom and patient set-up during CT-scan. . . . . . . . . . . . . . . . . . 47
3.2 Pointsofmorphing:head,greatertrochanter,underbelowgreatertrochanter,
and lesser trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.3 Points of morphing:the four points on the basis of the femur: anterior,
posterior, medial and lateral. . . . . . . . . . . . . . . . . . . . . . . . . . . 54
List of Figures ix
3.4 Steps of morphing algorithm: (a) original template mesh, (b) original STL
mesh, (c) result from morphing the template mesh on the STL using RBF
method,(d)resultsafterprojection(c)on(b),(e)resultfromtheLaplacian
smoothing, (f) final result represented in a high quality mesh of the STL
geometry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.5 Representation of the regression line between experimental and predicted
strain [STM+07]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
3.6 BoneMatofthefemur,withtherangeofYoung’smodulusbetween18000MPa
and the maximum value obtained from the software (19832 MPa). . . . . . 59
3.7 final structure of VME data tree (final structure of msf file).. . . . . . . . . 60
3.8 TF_IF_CH reference system. . . . . . . . . . . . . . . . . . . . . . . . . . . 61
3.9 CHA reference system; blue line is z-axis, red line is x-axis and green line
is y-axis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.10 Disposition of the Ansys key-points on CHA reference system. . . . . . . . 62
3.11 Frontal plane and transversal plane. . . . . . . . . . . . . . . . . . . . . . . 63
3.12 Femur’s local coordinate system and keypoints. . . . . . . . . . . . . . . . . 66
3.13 Representetion of the nominal direction of load. . . . . . . . . . . . . . . . . 67
3.14 Representetion of all direction of load. . . . . . . . . . . . . . . . . . . . . . 67
4.1 Visualization of the distribution of principal deformation on the femur (an-
terior view). The highest deformation is located on the top of the neck. . . 72
4.2 Visualization of the maximum strain point in posterior view of the femur. . 73
4.3 Box plot of BMD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.4 Box plot of FRAX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.5 Box plot of Strength. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
4.6 Box plot of WorkFlow 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
4.7 ROC curve of BMD. AUC is of 0:73. . . . . . . . . . . . . . . . . . . . . . . 79
4.8 ROC curve of FRAX. AUC is of 0:64. . . . . . . . . . . . . . . . . . . . . . 79
4.9 ROC curve of strength. AUC is of 0:72. . . . . . . . . . . . . . . . . . . . . 80
4.10 ROC curve of WF2. AUC is of 0:75. . . . . . . . . . . . . . . . . . . . . . . 80
4.11 ROC curve of strength, WF2, N_BMD, TH_BMD and FRAX. AUC is of
0:84. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.12 ROC curve of strength and FRAX. AUC is of 0:74. . . . . . . . . . . . . . . 83
4.13 ROC curve of WF2 and FRAX. AUC is of 0:76.. . . . . . . . . . . . . . . . 83
x List of Figures
4.14 ROC curve of strength, WF2, and FRAX. AUC is of 0:80. . . . . . . . . . . 84
4.15 ROC curve of strength and WF2. AUC is of 0:80. . . . . . . . . . . . . . . 84
4.16 ROC curve of strength, WF2, N_BMD and TH_BMD. AUC is of 0:83. . . 85
1 Representation of a box plot. The dots indicate the outliers.. . . . . . . . . 96
2 Representation of Mann-Whitney method. In (a) the different treatment
cause different effects, while in (b) they don’t produce any differences. . . . 97
3 Gaussian distribution of two population completely separated. . . . . . . . 101
4 Gaussian distribution of two population with overlapping area. . . . . . . . 101
5 Contingency table.TP represents the true positive results, TN represents
the true negative results, FP represents the false positive results and FN
represents the false negative results. . . . . . . . . . . . . . . . . . . . . . . 102
6 Representation of the ROC curve as a function of specificity (Sp) and sen-
sitivity (Se). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
7 Representation of the AUC, the area under ROC curve. . . . . . . . . . . . 104
8 Logistic function with (cid:12) =(cid:0)1 and (cid:12) =2. . . . . . . . . . . . . . . . . . . 105
0 1