Background Transthyretin amyloid (ATTR) amyloidosis is a systemic disorder caused by amyloid deposits formed by misfolded transthyretin (TTR) monomers. Two main forms exist – wild-type and hereditary ATTR amyloidosis, the latter associated with TTR gene mutations. Wild-type ATTR amyloidosis has a late onset and primarily cardiac manifestations, whereas hereditary ATTR amyloidosis is a rare autosomal dominant condition with a considerable phenotypic diversity. Both disorders are present all over the world, but endemic areas of the hereditary form are found in Sweden, Portugal, Brazil and Japan. Gastrointestinal (GI) complications are common in hereditary ATTR amyloidosis and play an important role in the patients’ morbidity and mortality. Malfunction of the autonomic and enteric nervous systems has been proposed to contribute to the GI disturbances, but the underlying mechanisms have not been fully elucidated. The aims of this thesis were to assess the prevalence of GI disturbances for different subtypes of ATTR amyloidosis, to further explore the mechanisms behind these disturbances, and to evaluate the outcome of the patients’ GI function after liver transplantation, which currently is the standard treatment for hereditary ATTR amyloidosis. Methods The Transthyretin Amyloidosis Outcomes Survey (THAOS) is the first global, multicenter, longitudinal, observational survey that collects data on patients with ATTR amyloidosis. THAOS enrollment data were used to assess the prevalence of GI symptoms and to evaluate their impact on nutritional status (mBMI) and health-related quality of life (EQ-5D Index Score). Data from routine investigations of heart-rate variability and cardio-vascular response to tilt tests were utilized to evaluate the impact of autonomic neuropathy on the scintigraphically measured gastric emptying half-times in Swedish patients with hereditary ATTR amyloidosis. Gastric wall autopsy specimens from Japanese patients with hereditary ATTR amyloidosis and Japanese non-amyloidosis controls were analyzed with immunohistochemistry and computerized image analysis to assess the densities of interstitial cells of Cajal (ICC) and nervous tissue. Data from gastric emptying scintigraphies and validated questionnaires were used to evaluate the outcome of Swedish patients’ GI function after liver transplantation for hereditary ATTR amyloidosis. Results Sixty-three percent of the patients with TTR mutations and 15 % of those with wild-type ATTR amyloidosis reported GI symptoms at enrollment into THAOS. Subsequent analyses focused on patients with TTR mutations and, among them, unintentional weight loss was the most frequent symptom (32 %) followed by early satiety (26 %). Early-onset patients (<50 years of age) reported GI symptoms more frequently than late-onset cases (70 % vs. 50 %, p <0.01), and GI symptoms were more common in patients with the V30M mutation than in those with non-V30M mutations (69 % vs. 56 %, p <0.01). Both upper and lower GI symptoms were significant negative predictors of nutritional status and health-related quality of life (p <0.01 for both). Weak but significant correlations were found between gastric emptying half-times and the function of both the sympathetic (rs = -0.4, p <0.01) and parasympathetic (rs = -0.3, p <0.01) nervous systems. The densities of c-Kit-immunoreactive ICC were significantly lower in the circular (median density 0.0 vs. 2.6, p <0.01) and longitudinal (median density 0.0 vs. 1.8, p <0.01) muscle layers of the gastric wall in patients compared to controls. Yet, no significant differences in protein gene product 9.5-immunoreactive nervous cells were found between patients and controls either in the circular (median density 3.0 vs. 6.8, p = 0.17) or longitudinal (median density 1.4 vs. 2.5, p = 0.10) muscle layers. Lastly, the patients’ GI symptoms scores had increased slightly from before liver transplantation to the follow-ups performed in median two and nine years after transplantation (median score 7 vs. 10 vs. 13, p <0.01). However, their gastric emptying half-times (median half-time 137 vs. 132 vs. 125 min, p = 0.52) and nutritional statuses (median mBMI 975 vs. 991 vs. 973, p = 0.75) were maintained at follow-ups in median two and five years after transplantation. Conclusion GI disturbances are common in hereditary ATTR amyloidosis and have a negative impact on the patients’ nutritional status and health-related quality of life. Fortunately, a liver transplantation appears to halt the progressive GI involvement of the disease, although the patients’ GI symptoms tend to increase after transplantation. An autonomic neuropathy and a depletion of gastrointestinal ICC seem to contribute to the GI disturbances, but additional factors must be involved.

High interstitial fluid pressure (IFP) in tumours is recognized as a barrier to drug delivery resulting in reduced efficacy. High IFP impedes the normal process of convective fluid flow (CFF) from blood vessels into the interstitium. The aim of this study was to develop an in vitro model that could be used to measure CFF and to study its effects on drug delivery. The model consists of a transwell cell culture insert which supports the growth of multicell layers (MCL) on collagen coated membranes. A graduated tube is inserted into the transwell and a pressure gradient is applied across the membrane by raising the volume of medium in the tube above that of the bottom chamber. CFF is determined by measuring the weight of medium in the bottom chamber as a function of time. CFF was inversely proportional to MCL thickness and 41.1±3.6µm thick MCL has completely stopped CFF. Using a physiologically relevant hydrostatic pressure of 28mmHg, a CFF of 21µL/min was recorded using a DLD-1 MCL that was 12.21±3.2µm thick. Under these conditions, the rates of penetration of doxorubicin, imatinib and gefitinib were respectively 42, 26 and 13 folds greater than when no CFF exists. Reversing the CFF so that it opposed the drug diffusion gradient significantly impairs drug penetration. In conclusion, a novel in vitro model for assessing the impact of CFF on drug delivery has been developed. This model could be used to evaluate strategies designed to increase drug delivery to solid tumours by modifying the CFF.

No description available.

Hypertension and salt-sensitivity are independent risk factors for cardiovascular disease. Although both conditions are idiopathic, they develop due to a complex interplay between susceptibility genes and environmental factors. Given that the kidney plays an important role in regulating blood pressure, in particular, by maintaining sodium and water balance via pressure-natriuresis, it is not surprising that disturbances in the proper functioning of this intrarenal mechanism have been linked to these conditions. Although direct coupling of changes in renal arterial pressure (RAP) to renal interstitial hydrostatic pressure (RIHP) and consequent sodium excretion is well established, few studies have characterized the moment-to-moment aspects of this process. Thus, the main focus of the research presented herein was to characterize the moment-to-moment RAP-RIHP relationship, and assess the functioning of this intrarenal mechanism in various animal models of genetic and environmentally-induced hypertension and/or salt-sensitivity. In adult normotensive rats, the response time of RIHP to acute changes in RAP was rapid (<2 seconds), and the moment-to-moment RAP-RIHP relationship was linear over a wide range of pressures. Additionally, the functioning of this relationship was not affected by inhibition of the renin-angiotensin system and autonomic nervous system. Further, the acute RAP-RIHP relationship was impaired in hypertension and/or salt-sensitivity. Specifically, animals with a hypertensive phenotype (i.e. young spontaneously hypertensive rats [SHR] and pro-atrial natriuretic peptide gene-disrupted mice [ANP -/-]) displayed a rightward shift in the moment-to-moment pressure-natriuresis curve towards higher RAP. This rightward shift was associated with increased structurally-based vascular resistance properties in the hindlimb of young SHR versus their normotensive controls. Salt-sensitive phenotypes were associated with a blunting of this acute mechanism. Specifically, this blunting was evident in both the ANP -/-, a transgenic model of salt-sensitive hypertension, and in adult perinatal iron deficient (PID) rats, a developmentally programmed model of salt-sensitivity. It appears that a blunting in the RAP-RIHP relationship is influenced by an imbalance of key blood pressure modulating factors (e.g. ANP). Further, visceral obesity was associated with salt-sensitivity in PID rats; however the mechanism(s) are yet to be elucidated. Novel methodologies (MRI, abdominal girth) were developed for non-invasive assessment of visceral obesity to aid future research. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2010-05-12 10:11:21.197

No description available.

This thesis encompasses the development and testing of an interstitial photodynamic therapy (iPDT) system for the treatment of prostate cancer. It begins with the optical characterization of a novel photosensitizer (SL-052) followed by a study of tissue optics as it applies to iPDT. The design and integration of a time-fractionated light delivery system with real-time spectral detection is then examined. An optical phantom test medium is formulated and in vitro system operation and testing is performed. Finally, in vivo experiments are performed on animal models with a focus on canine prostate iPDT. Unique optical results with dosimetric relevance are discovered and investigated. This includes metrics for optically measuring local in vivo SL-052 concentrations in real-time as well as novel oscillatory drug photobleaching and recovery behavior during time-fractionated light delivery. / Photonics and Plasmas

No description available.

The aims of this thesis were to: 1) develop a new method for the determination of interstitial pH at rest and during exercise in vivo, 2) systematically explore the effects of different ingestion regimes of 300 mg.kg-1 sodium citrate on blood and urine pH at rest, and 3) to combine the new interstitial pH technique with the findings of the second investigation in an attempt to provide a greater understanding of H+ movement between the extracellular compartments. The purpose of the first study was to develop a method for the continuous measurement of interstitial pH in vastus lateralis was successfully developed using microdialysis and 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). To avoid the presence of an artificial alkalosis during exercise, it was necessary to add 25 mM HCO3- to the perfusate. The outlet of the probe was cut less than 10 mm from the skin and connected to a stainless steel tube completing the circuit to a microflow-through cuvette (8 fÝl) within a fluorescence spectrophotometer. This prevented the loss of carbon dioxide from the dialysate and any subsequent pH artefact. Interstitial pH was collected from six subjects before, during and after five minutes of knee-extensor exercise at three intensities 30, 50, and 70 W. Mean,,bSEM interstitial pH at rest was 7.38,,b0.02. Exercise reduced interstitial pH in an almost linear fashion. The nadir value for interstitial pH at 30, 50 and 70 W exercise was 7.27, 7.16 and 7.04, respectively. The lowest pH was obtained 1 min after exercise, irrespective of workload, after which the interstitial pH recovered in a nearly exponential manner. The mean half time of interstitial recovery was 5.2 min. The changes in interstitial pH exceeded the changes in venous blood pH. This study demonstrated that interstitial pH can be measured using microdialysis and that it is continuously decreased during muscle activity. The purpose of the second study was to establish an optimal ingestion regime for the ingestion of 300 mg.kg-1 of sodium citrate and maximise the alkalotic effect while minimising any side effects. Increasing the effectiveness of alkali ingestion may lead to further increases in muscle performance. Ingesting 300 mg.kg-1 sodium citrate at a rate of 300 mg.min-1 was identified as the optimal ingestion regime to maximise alkalosis at rest, which occurred 3.5 h post-ingestion. This was determined by monitoring eight human subjects ingesting 300 mg.kg-1 sodium citrate at five different rates, control (no ingestant), bolus, 300, 600 and 900 mg.kg.min-1 on five days separated by at least 48 hours. Sodium citrate was ingested in capsule form with water ad libitum, with the exception of bolus, which was combined with 400 ml less than 25 percent orange juice and consumed in less than 1 min. Arterialised blood (mean 71.3,,b3.5 mmHg) acid-base and electrolyte status was assessed via the withdrawal of ~5 ml of blood every 30 min across an eight hour duration, placed on ice and analysed within five minutes. No alkalotic difference was found between ingestion rates (mean 7.445,,b0.004, 7.438,,b0.004 and 7.442,,b0.004 for 300, 600 and 900 mg.min-1, respectively). All experimental ingestion regimes were associated with elevations in [HCO3-] (29.6, 29.7, 29.8, 29.9 and 26.3 mmol.l-1 for bolus, 300, 600, 900 and control, respectively). The 300 ingestion regime had the greatest impact on [H+], a 0.66 meq.l-1,,e10-8 change. Bolus ingestion (3.93,,b0.08 mmol.l-1) of sodium citrate had no effect on control (4.06,,b0.08 mmol.l-1) blood [K+], however, 300 mg.min-1 decreased blood [K+] (p less than 0.05). There was no effect of sodium citrate on blood [Cl-], but after 2.5 h blood [Cl-] was lower than pre-ingestion values (p less than0.05). All ingestion rates of sodium citrate increased (p less than 0.05) urine pH above control. This is the first study to investigate the effect of varying ingestion rates on acid-base status at rest in humans. The results suggest that ingesting sodium citrate in small doses in quick succession induce a greater blood alkalosis than the commonly practised bolus protocol. Using the interstitial pH technique described above and the optimal ingestion regime (300 mg.min-1) identified above, the final experiment was designed to assess the influence of sodium citrate ingestion on interstitial pH at both rest and during exercise. Five subjects ingested 300 mg.kg-1 sodium citrate at 300 mg.min-1 again in capsule form with water ad libitum. Prior to ingestion, each subject had a cannula placed into their cephalic vein and one microdialysis probe (CMA-60) inserted into their left thigh, orientated along the fibres of vastus lateralus. This probe was used for the measurement of pH as described above. At the end of this period, an exercise protocol required five subjects to perform light exercise (10 W) for 10 min, before starting an intense exercise period (~90-95% leg VO2peak) to exhaustion followed by a 15 min recovery period. Dialysate and blood samples were collected across all periods. Mean,,bSEM interstitial pH for placebo and alkalosis were 7.38,,b0.12 and 7.24,,b0.16, respectively. Sodium citrate ingestion was not associated with an interstitial alkalosis. An exercise induced acidosis was observed in the interstitium during placebo but not during alkalosis (p less than 0.05). Mean,,bSEM venous pH were 7.362,,b0.003 and 7.398,,b0.003 for placebo and alkalosis, respectively. Sodium citrate ingestion was not associated with a venous alkalosis. Sodium citrate ingestion was associated with an increase in mean,,bSEM venous [HCO3-] (placebo 25.5,,b0.2, alkalosis 28.1,,b0.2). This increase in the blood bicarbonate buffer system was not associated with an increase in time to exhaustion (placebo 352,,b71, alkalosis 415,,b171). This was the first study to investigate the effects of sodium citrate ingestion on interstitial pH. The results of this study demonstrated that an interstitial alkalosis does not ensue after alkali ingestion, however, it was associated with the lack of an exercise induced acidosis suggesting an improved pH regulation during exercise.

Image analysis techniques have been broadly used in computer aided diagnosis tasks in recent years. Computer-aided image analysis is a popular tool in medical imaging research and practice, especially due to the development of different imag- ing modalities and due to the increased volume of image data. Image segmenta- tion, a process that aims at identifying and separating regions of an image, is crucial in many medical applications, such as in identification (delineation) of anatomical structures and pathological regions, providing objective quantitative assessment and monitoring of the onset and progression of the disease. Multidetector CT (MDCT) allows acquisition of volumetric datasets with almost isotropic voxels, enabling visualization, characterization and quantification of the entire extent of lung anatomy, thus lending itself to characterization of Interstitial Lung Diseases (ILDs), often characterized by non uniform (diffuse) distribution in the lung volume. Interpretation of ILDs is characterized by high inter and intra- observer variability, due to lack of standardized criteria in assessing its complex and variable morphological appearance, further complicated by the increased vol- ume of image data being reviewed. Computer-Aided Diagnosis (CAD) schemes that automatically identify and char- acterize radiologic patterns of ILDs in CT images have been proposed to improve diagnosis and follow-up management decisions. These systems typically consist of two stages. The first stage is the segmentation of left and right Lung Parenchyma (LP) region, resulting from lung field segmentation and vessel tree removal, while the second stage performs classification of LP into normal and abnormal tissue types. The segmentation of Lung Field (LF) and vessel tree structures are crucial preprocessing steps for the subsequent characterization and quantification of ILD patterns. Systems proposed for identification and quantification of ILDpatterns havemainly exploited 2D texture extraction techniques, while only a few have investigated 3D texture features. Specifically, texture feature extraction methods that have been exploited towards lung parenchyma analysis are: first order statistics, grey level co-occurrence matrices, gray level run length matrices, histogram signatures and fractals. The identification and quantification of lung parenchyma into normal and abnormal tissue type has been achieved by means of supervised classification tech- niques (e.g. Artificial Neural Networks, ANN, Bayesian classifier, linear discrimi- nant analysis (LDA) and k-Nearest Neighboor (k-NN). However, the previously proposed identification and quantification schemes in- corporate preprocessing segmentation algorithms, effective on normal patient data. In addition the effect of the preprocessing stages (i.e. segmentation of LF and ves- sel tree structures) on the performance of ILD characterization and quantification schemes has not been investigated. Finally, the complex interaction of such automated schemes with the radiologists remains an open issue. The current thesis deals with identification and quantification of ILD in lung CT. The thesis aims at optimizing all major steps encountered in a computer aided ILD quantification scheme, by exploiting 3D texture feature extraction techniques and supervised and unsupervised pattern classification schemes to derive 3D disease segments. The specific objectives of the current thesis are focused on: • Development of LF segmentation algorithms adapted to pathology. • Development of vessel tree segmentation adapted to presence of pathology. • Development of ILD identification and quantification algorithms. • Investigation of the interaction of an ILD identification and quantification scheme with the radiologist, by an interactive image editing tool. / Η Διάμεση Νόσος (ΔΝ) του πνεύμονα αποτελεί το 15% των παθήσεων του πνεύμονα που εμφανίζονται στην κλινική πρακτική. Η ΔΝ επηρεάζει κυρίως το πνευμονικό παρέγχυμα και εμφανίζεται στις εικόνες Υπολογιστικής Τομογραφίας (ΥΤ) του πνεύμονα με την μορφή διάχυτων περιοχών χαρακτηριστικών προτύπων υφής που παρεκκλίνουν από αυτό του φυσιολογικού παρεγχύματος. Η Πολυτομική Υπολογιστική Τομογραφία (ΠΥΤ) επιτρέπει την απόκτηση τρισδιάστατων απεικονίσεων με σημαντική μείωση του χρόνου λήψης και αποτελεί την απεικονιστική τεχνική επιλογής για την ποσοτικοποίηση και τη διάγνωση της ΔΝ. Η διάγνωση της ΔΝ χαρακτηρίζεται από μειωμένη διαγνωστική ακρίβεια χαρακτηρισμού και ακρίβεια ποσοτικοποίησης έκτασης ακόμα και για τον έμπειρο ακτινολόγο, αλλά και από χαμηλή επαναληψιμότητα. Η δυσκολία διάγνωσης οφείλεται στη μειωμένη ικανότητα του ανθρώπινου παράγοντα ως προς το καθορισμό έκτασης των προτύπων υφής λόγω ομοιότητας ακτινολογικής εμφάνισης τους σε συνδυασμό με το φόρτο εργασίας του ακτινολόγου και τον αυξημένο όγκο δεδομένων της ΠΥΤ. Αυτοματοποιημένα συστήματα ανάλυσης εικόνας μπορούν να αντιμετωπίσουν τα παραπάνω προβλήματα παρέχοντας σημαντική υποβοήθηση στο έργο της διάγνωσης και παρακολούθησης της νόσου. Η ανάπτυξη αυτοματοποιημένων συστημάτων ανάλυσης εικόνας για υποβοήθηση διάγνωσης στην ΥΤ του πνεύμονα έχει αποτελέσει θέμα εκτεταμένης έρευνας την τελευταία δεκαετία με ένα μικρό τμήμα της να επικεντρώνεται στο χαρακτηρισμό και ποσοτικοποίηση της έκτασης της ΔΝ. Σημαντικά στάδια προεπεξεργασίας των συστημάτων αυτών αποτελούν οι τμηματοποίησεις των Πνευμονικών Πεδίων (ΠΠ) και του αγγειακού δένδρου για τον καθορισμό του προς ανάλυση όγκου του πνευμονικού παρεγχύματος. Τα έως σήμερα προταθέντα συστήματα αυτόματης ανίχνευσης και ποσοτικοποίησης της έκτασης της ΔΝ αξιοποιούν κυρίως μεθόδους ανάλυσης δισδιάστατης (2Δ) υφής εικόνας, ενώ μόνο δύο μελέτες έως σήμερα έχουν αξιοποιήσει ανάλυση 3Δ υφής. Συγκεκριμένα, μέθοδοι ανάλυσης υφής εικόνας που έχουν αξιοποιηθεί είναι: στατιστική 1ης τάξης (ιστόγραμμα), μήτρες συνεμφάνισης αποχρώσεων του γκρι (Grey level Co-occurrence Matrices), μήτρες μήκους διαδρομής απόχρωσης του γκρι (Gray Level Run Length Matrices), υπογραφές ιστογράμματος και Fractals. Ο χαρακτηρισμός και η ποσοτικοποίηση περιοχών του πνευμονικού παρεγχύματος που αντιστοιχούν σε φυσιολογικό παρέγχυμα και υποκατηγορίες παθολογίας υλοποιείται με μεθόδους επιβλεπόμενης ταξινόμησης προτύπων όπως: τεχνητά νευρωνικά δίκτυα (Artificial Neural Networks, ΑΝΝ), Bayesian ταξινομητής, ανάλυση γραμμικού διαχωρισμού ( Linear Discriminant Analysis, LDΑ) και ταξινομητής πλησιέστερου γείτονα (k-Nearest Neighboor, k-NN). Στα έως σήμερα προταθέντα συστήματα, η τμηματοποίηση των ΠΠ υλοποιείται με συμβατικές μεθόδους τμηματοποίησης με βάση τις αποχρώσεις του γκρί (τιμές έντασης) εικονοστοιχείων. Ανοικτό ζήτημα παραμένει και η αξιολόγηση της επίδρασης των σταδίων προ-επεξεργασίας (τμηματοποίηση ΠΠ και αγγειακού δένδρου) στην ακρίβεια συστημάτων χαρακτηρισμού και ποσοτικοποίησης της έκτασης της ΔΝ. Τέλος, η αξιολόγηση της αλληλεπίδρασης αυτόματων συστημάτων ποσοτικοποίησης και ακτινολόγου στη λήψη αποφάσεων χαρακτηρισμού και ποσοτικοποίησης της έκτασης που αφορούν την ΔΝ δεν έχει διερευνηθεί. Η παρούσα διδακτορική διατριβή επικεντρώνεται στην ανάπτυξη ολοκληρωμένου συστήματος ανάλυσης εικόνας το οποίο χαρακτηρίζει και ποσοτικοποιεί την έκταση περιοχών με ΔΝ σε απεικονίσεις ΠΥΤ θώρακος, στοχεύοντας στη βελτιστοποίηση όλων των σταδίων του, καθώς και στην αξιολόγηση της συμβολής του συστήματος στην λήψη διαγνωστικών αποφάσεων. Για το σκοπό αυτό διερευνώνται τεχνικές 3Δ ενίσχυσης εικόνας, 3Δ τμηματοποίησης εικόνας καθώς και 3Δ χαρακτηριστικά υφής εικόνας σε συνδυασμό με επιβλεπόμενα και μη επιβλεπόμενα συστήματα ταξινόμησης. Συγκεκριμένα η συμβολή της παρούσας διατριβής επικεντρώνεται στα ακόλουθα: • Ανάπτυξη μεθόδων τμηματοποίησης των ΠΠ και του αγγειακού δένδρου παρουσία παθολογίας. • Διερεύνηση της συμβολής αλγορίθμων εξαγωγής 3Δ υφής εικόνας στην ακρίβεια μεθόδων ταξινόμησης προτύπων ΔΝ. • Βελτιστοποίηση μεθόδων χαρακτηρισμού και ποσοτικοποίησης έκτασης με χρήση τεχνικών επιβλεπόμενης και μη επιβλεπόμενης ταξινόμησης. • Αξιολόγηση της επίδρασης των σταδίων προεπεξεργασίας στην ακρίβεια συστημάτων ποσοτικοποίησης. • Αξιολόγηση της συμβολής συστημάτων ποσοτικοποίησης στη διάγνωση της ΔΝ.

As doenças pulmonares intersticiais difusas caracterizam-se pela presença de um distúrbio ventilatório restritivo cuja intensidade está associada ao grau de extensão do comprometimento intersticial e consequentemente ao estágio da doença. As provas de função pulmonar em conjunto com o grau de comprometimento intersticial na TCAR são os principais métodos de avaliação utilizados para determinar o estágio da doença, bem como para acompanhar sua progressão e a resposta terapêutica. A densitovolumetria pulmonar realizada através da TC Helicoidal consiste em uma técnica objetiva e mais precisa que permite calcular a proporção de volume de pulmão com densidade aumentada pelo acometimento por fibrose sobre o volume de pulmão com densidade normal, ou seja, sem acometimento significativo dos interstícios. Na literatura, sugere-se –870 UH como o limiar de separação ideal para quantificação de fibrose pulmonar por tomografia computadorizada, acima do qual o pulmão seria considerado como apresentando aumento de densidade pela presença de fibrose ou de atenuação em vidro-fosco. O presente estudo comparou o limiar fixo em –870UH com a utilização de um limiar subjetivo ou variável selecionado com o auxílio de máscara de densidades em 30 pacientes com comprovação histológica FPI em relação as provas de função pulmonar. A correlação dos resultados da densitovolumetria pulmonar utilizando o limiar fixo (-870 HU) com as provas de função pulmonar foram de r= 0,265 com o VEF1, r=-0,450 com a CVF, r=-0,705 com a CPT e r= -0,305 com a DCO. Em comparação, as correlações entre os resultados da densitovolumetria pulmonar estabelecidos com base na seleção subjetiva de um limiar subjetivo foram: r= –0,347 com o VEF1, r= - 0,534 com a CVF, r= -0,734 com a CPT e r= –0,413 com a DCO. Tanto as medidas objetivas como subjetivas da extensão da fibrose realizadas pela densitovolumetria apresentaram boa correlação com as medidas funcionais que expressam restrição. As correlações foram fracas, quando correlacionadas com medidas funcionais que não expressam a extensão da fibrose pulmonar. A densitovolumetria pode proporcionar uma técnica mais precisa que a simples análise subjetiva das imagens de tomografia computadorizada de alta resolução em pacientes com FPI, sendo assim mais efetiva na avaliação evolutiva de cada paciente. / Diffuse interstitial pulmonary diseases are characterized by restrictive lung disorders whose intensity is associated with the extent of interstitial involvement and, consequently, the stage of the disease. Pulmonary function tests and HRCT assessment of the degree of interstitial involvement are the primary methods to establish the stage of the disease, to follow up its progression, and to evaluate therapeutic response. Pulmonary densitovolumetry using helical CT is an objective and accurate technique to calculate the proportion of volume of lung with increased density due to fibrosis with relation to volume of lung with normal density, that is, without significant interstitial involvement. Studies in the literature suggest - 870 UH as the ideal segmentation threshold to assess pulmonary fibrosis using CT; above this value, increased density due to fibrosis or ground-glass opacity should be considered. In this study, the use of a -870 HU fixed threshold was compared with the use of a subjective or variable threshold selected with the aid of a density mask in 30 patients with a histologic diagnosis of IPF, and results were correlated with pulmonary function test results. Correlations between pulmonary densitovolumetry using the fixed threshold (-870 HU) and pulmonary function tests were r= 0.265 for FEV1, r=-0.450 for FVC, r=-0.705 for TLC and r= -0.305 for DLCO. When pulmonary densitovolumetry with selection of a subjective threshold was used, results were: r= –0.347 for FEV1, r= -0.534 for FVC, r= -0.734 for TLC and r= –0.413 for DLCO. Both objective and subjective measurements of the extent of fibrosis using densitovolumetry had a good correlation with results of functional tests that indicate restriction. Correlations were weak with functional measurements that do not indicate the extent of pulmonary fibrosis. Densitovolumetry may be a more accurate technique than the simple subjective analysis of high-resolution CT images in patients with IPF, and may be, therefore, more effective in the evaluation of disease progression.