Measurement of nutrients transport into intervertebral discs

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Measurement of nutrients transport into
intervertebral discs

• Some results from our clinical study carried out
  in Oxford Physiology and the Nuffield Orthopaedic
  Centre

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What we know. What we want to do.

• Disc degeneration is linked to nutrient transport
  limitations by indirect evidence e.g.
  interruption of disc blood supply by disease,
  etc, is associated with degenerate discs.
• Nutrient transport limitation is a plausible
  theory because healthy discs are the largest
  avascular human tissue
• However, we hope to link disc degeneration more
  directly to transport limitations through this
  study

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Hypothesis

• The disc health or pathology depends on two
  inextricably related components
• Metabolic activity of the cells
• Diffusion rate through the extra-cellular matrix
• In order to quantify disc pathology, both these
  parameters must be quantified and compared to a
  selected nominally healthy control.

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Materials and Methods
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Electrode System

• O2 and N2O measured Amperometrically.
• Electrode is 125 µm Ag wire in 18-gauge needle.
• Ag/AgCl Reference
• Potentiostat / pre-amplifier
• All in-house manufacture

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Data collected and MRI grading

• Raw data collected includes-
• Time since applying anaesthetic gas and the gas
  make-up
• Concentration values for nitrous and oxygen in
  the disc
• Disc height, location and MRI grade
• Electrode position assumed as centre of nucleus
  (weakness)
• Various patient behavioural/lifestyle
  characteristics
• If possible, patient blood and tissue samples are
  also collected
• MRI grades as per Boos Spine paper are shown

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Data Analysis

• Non-Viable Tissue
• Consumes less O2
• Contains N2O (from General Anaesthetic)

• Viable Tissue
• Consumes O2
• Contains N2O (from General Anaesthetic)

• O2 1/a Cellular Activity
• N2O a Matrix Perfusion

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Viable Tissue
N2O
O2
O2
O2
O2
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Non-Viable Tissue
N2O
O2
O2
O2
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Some patient characteristics

• So far measurements were performed on 20
  consenting patients during routine discectomy
  operation. Approx 60 male.
• Age range 28-70yrs Most cases at 28-45years.
• Most trouble at L4-5 level, followed by L5-S1
  level.
• Large variety of occupations Mixture of
  Ex/Non/Smokers.
• Measurements caused insignificant delay to
  procedure.

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How useful is this type of study?

• This study confirms some known results, e.g.
  shows how patient age and macroscopic disc health
  (currently taken as MRI grade) are not
  correlated. So older patients can have less
  degenerate discs and vice versa.

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Whats new and useful?

• Transport efficiency defined measured-to-ideal
  nitrous conc. Ideal concentration present at
  same conditions in healthy disc. Healthy disc
  two year old bovine caudal disc.
• This parameter can help diagnose blood vessel
  invasion (TEgt100) and indicates matrix transport
  condition.

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Anything else useful?

• Cellular Activity defined residual disappearance
  of oxygen after determining real transported
  values from the nitrous data. This parameter
  essentially shows how much cellular activity was
  present.

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A new, old story.

• This graph just gives another version of the old
  story age is not a good indicator of disc
  pathology. Just because youre older doesnt mean
  your disc is not young.

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An interesting trend in the results
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Comments and Opportunities

• MRI grade patient age are unreliable indicators
  of disc health. Thus a reliable method is needed
  for rapid biological assessment of discs in vivo.
• Disc health can be quantified with the use of
  these electrode biosensors without delaying
  routine treatments. Same technique is also being
  applied into shoulder tendon degeneration studies
  with great success.
• These sensors should enable selection of
  appropriate treatments in the future, such as
  tissue engineering, growth factors and gene
  therapy..and other clever things.
• These biosensors still need further development
  for ease-of-use in diagnosis and prognosis. Also
  some further biological analysis needs
  development to add value to the method (e.g.
  cut-offs). However, it does seem promising.

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Thank you

• Appreciation to-
• The Nuffield Orthopaedic Centre, Oxford for
  granting ethical committee approval for our
  research.
• Our co-researcher and surgeon, Jeremy Fairbank
  for access to patients and advising on all
  clinical issues.
• EPSRC and EU Quality-of-Life grant for funding.

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2-D Modelling of Tissue Perfusion
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Transport and Activity Calculations
Matrix Perfusion Nitrous measurements
Cellular Activity Oxygen measurements
Ro2